Benzimidazoles, medicaments containing these compounds and processes for their preparation

ABSTRACT

The invention relates to benzimidazoles of the formula ##STR1## in which R 1  to R 4  are as defined in claim 1, 
     1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties. 
     In particular, the novel compounds are angiotensin II antagonists.

This is a continuation of application Ser. No. 08/608,353, filed Feb.28, 1996, now abandoned, which is a divisional of application U.S. Ser.No. 08/227,291, filed on Apr. 13, 1994, now U.S. Pat. No. 5,541,229which is a continuation of application U.S. Ser. No. 07/979,400, filedon Nov. 19, 1992, now abandoned, which is a continuation of applicationU.S. Ser. No. 07/750,175, filed on Aug. 26, 1991, now abandoned, whichis a continuation of application U.S. Ser. No. 07/505,967, filed on Apr.6, 1990, now abandoned.

The present invention relates to 1 and 3 isomers of the benzimidazolesof the formula ##STR2## and, provided that R₁ and R₂ are not both ahydrogen atom at the same time or do not both have the same meanings inthe 4 and 7 position or in the 5 and 6 position, the 1 and 3 isomermixtures thereof and the addition salts thereof, in particular for thepharmaceutical use of their physiologically acceptable addition saltswith inorganic or organic acids or bases.

In the above formula I

R₁ denotes a hydrogen, fluorine, chlorine or bromine atom,

an alkyl group having 1 to 4 carbon atoms, which may be substituted by ahydroxy, alkoxy, amino, alkylamino, dialkylamino or acylamino group,

an alkoxy group having 1 to 4 carbon atoms, which may be substituted inthe 2, 3 or 4 position by a hydroxy, alkoxy, amino, alkylamino,dialkylamino or imidazolyl group,

a hydroxy, phenylalkoxy, acyloxy, trifluoromethylsulphonyloxy,alkylaminocarbonyloxy, dialkylaminocarbonyloxy,cycloalkylaminocarbonyloxy, cycloalkylalkylaminocarbonyloxy,arylaminocarbonyloxy, aralkylaminocarbonyloxy, alkoxycarbonyloxy,cycloalkylalkoxycarbonyloxy, cycloalkylalkoxycarbonyloxy,aryloxycarbonyloxy, aralkoxycarbonyloxy, trifluoromethyl, cyano, nitro,alkylmercapto, alkylsulphinyl, alkylsulphonyl, aminosulphonyl,alkylaminosulphonyl, dialkylaminosulphonyl, arylaminosulphonyl,acylaminosulphonyl or acyl group,

an amino group, which may be monosubstituted by an imidazolylalkyl,dialkylaminoalkanoyl, acyl, cycloalkoxycarbonyl,cycloalkylalkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl ortrifluoroacetyl group, by a bicyclic or tricyclic alkyl group having 7to 11 carbon atoms, by an alkylsulphonyl group having 1 to 4 carbonatoms, by an alkoxycarbonyl group having a total of 2 to 7 carbon atomsor by a thiazolidin-3-yl-carbonyl group substituted by an alkoxycarbonylgroup,

an alkylamino group having 1 to 6 carbon atoms, which may be substitutedat the nitrogen atom by an alkyl, alkylsulphonyl or acyl group, wherein,if the acyl group is an alkanoyl group, it may be additionallysubstituted by an alkoxy group, and the alkyl substituent may besubstituted at position 2 by a hydroxy, alkoxy or arylamino group,

an amino group monosubstituted or disubstituted by a cycloalkyl,cycloalkylalkyl, phenylalkyl or phenyl group, wherein the substituentsmay be the same or different,

an N-alkyl-cycloalkylamino, N-alkyl-cycloalkylalkylamino,N-alkyl-phenylalkylamino or N-alkyl-phenylamino group,

a pyrrolidino, piperidino or hexamethyleneimino group optionallysubstituted by an alkyl, cycloalkyl or phenyl group,

an N-alkoxycarbonyl-alkylamino, N-cycloalkoxycarbonylalkylamino,N-cycloalkylalkoxycarbonyl-alkylamino, N-aryloxycarbonyl-alkylamino orN-aralkoxycarbonylalkylamino group, in which the alkyl group may contain1 to 6 carbon atoms in each case, an alkoxycarbonylamino,cycloalkoxycarbonylamino, cycloalkylalkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, acylamino oralkylsulphonylamino group substituted at the nitrogen atom by acycloalkyl, cycloalkylalkyl or aralkyl group,

a carbonyl group, which is substituted by an alkyl group which issubstituted in the 2 or 3 position by a hydroxy, alkanoyloxy oralkylamino group, by a hydroxycarbonylalkyl, hydroxy, alkoxy, amino,cycloalkylamino, cycloalkylalkylamino, arylamino or aralkylamino group,by an alkylamino group substituted in the 2 or 3 position by anarylamino group, or by an alkylamino group having 1 to 5 carbon atomsand optionally substituted by a carboxy group in the alkyl part, whichmay be substituted in each case additionally at the nitrogen atom by analkyl group,

an aminoacetylamino group optionally substituted by an alkoxycarbonylgroup having a total of 2 to 5 carbon atoms,

an aminocarbonylamino or aminothiocarbonylamino group, which may bemonosubstituted, disubstituted or trisubstituted by an alkyl grouphaving 1 to 20 carbon atoms, by an alkenyl or alkynyl group having 3 to5 carbon atoms in each case, by a bicyclic or tricyclic alkyl grouphaving 7 to 11 carbon atoms, by a cycloalkyl, cycloalkylalkyl, aralkylor aryl group, wherein the substituents may be the same or different,and a methylene group in a cycloalkyl radical having 5 to 7 carbon atomsmay be replaced by an oxygen atom, and an alkyl group may be substitutedin the 4, 5 or 6 position by a hydroxy, alkanoyl or trifluoroacetylgroup,

a cycloalkyleneiminocarbonylamino group having 4 to 6 carbon atoms inthe cycloalkyleneimino moiety or a morpholinocarbonylamino group, whichmay both be substituted at the amino nitrogen by an alkyl group having 1to 20 carbon atoms, or by a cycloalkyl, cycloalkylalkyl, aralkyl or arylgroup,

a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino,2-carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, whilst a carbonyl group ina phthalimino group may be replaced by a methylene group and a methylenegroup in a homophthalimino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted by one ortwo alkyl groups, and additionally the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, whilst thesubstituents may be identical or different, and at the same time theymay be partially or wholly hydrogenated, a bicycloalkane-3-carboxylicacid amino or bicycloalkene-3-carboxylic acid amino group substituted bya carboxy group in the 2-position, a bicycloalkane-2,3-dicarboxylic acidimino or bicycloalkene-2,3-dicarboxylic acid imino group, wherein thebicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms,may be substituted by 1, 2 or 3 methyl groups and an endomethylene groupmay be replaced by an oxygen atom, a glutaric acid imino or3-carboxy-n-propylene-carbonyl group wherein the n-propylene group maybe perfluorinated, substituted by one or two alkyl groups or by atetramethylene or pentamethylene group, or

a 5,7-dioxa-1H,3H-imidazo 1,5-c!thiazolyl group,

R₂ denotes the meanings for R₁ mentioned above, a 2-imidazolidon-1-yl or3,4,5,6-tetrahydro-2-pyrimidon-1-yl group optionally substituted in the3 position by an alkyl, cycloalkyl, cycloalkylalkyl or aralkyl group, ora tetrazolyl group or

R₁ and R₂ together with 2 carbon atoms of the neighbouring phenyl ringdenote a phenyl or 1-alkyl-3,3-dialkyl-2,3-dihydropyrrol-2-one group,

R₃ denotes a hydrogen, fluorine, chlorine or bromine atom,

an alkyl group having 1 to 6 carbon atoms, in which a methylene groupmay be replaced by an oxygen or sulphur atom, a sulphinyl, sulphonyl oralkylamino group, and a methyl group may be substituted by a hydroxy,alkoxy, amino, alkylamino or dialkylamino group, but wherein themethylene group next to the benzimidazole ring may not be replaced by asulphinyl or sulphonyl group, and when a methylene group is replaced anda methyl group is substituted at the same time, they must be separatedfrom one another by at least 2 carbon atoms,

an alkenyl or alkynyl group each having 3 to 5 carbon atoms,

a phenylalkyl group,

a cycloalkyl or cycloalkylalkyl group, in which the cycloalkyl moietymay contain 5 to 7 carbon atoms in each case,

an aryl, hydroxy or imidazolylalkylamino group,

an alkylamino group having 1 to 4 carbon atoms,

an aminocarbonyl group, which may be substituted by an alkyl orcycloalkyl group having 5 to 7 carbon atoms,

a 5-membered heteroaromatic ring, which contains an NH group, an oxygenor sulphur atom, wherein this 5-membered heteroaromatic ring mentionedabove may additionally contain a further 1 to 3N atoms, or a 6-memberedheteroaromatic ring, which may contain 1 or 2 nitrogen atoms, whereinthe 5-membered and 6-membered heteroaromatic rings mentioned above maybe substituted by one or, with the exception of the tetrazolyl group, bytwo alkyl groups,

R₄ denotes an amino, phthalimino, aminomethyl, cyano,tert.-butoxycarbonyl or 1-(triphenylmethyl)-tetrazolyl group, a groupcontaining a Bronsted acid or a radical which can be converted in vivoto a group containing a Bronsted acid,

R₅ denotes a hydrogen, fluorine, chlorine or bromine atom,

R₆ denotes a hydrogen atom or

R₅ and R₆ together with the two ortho position carbon atoms denote aphenyl group.

The term "a group containing a Bronsted acid" mentioned above especiallymeans in this case a carboxy, aminoacetylamino,trifluoromethylcarbonylamino, trifluoromethylcarbonylaminomethyl,trifluoromethylsulphonylamino, trifluoromethylsulphonylaminomethyl or1H-tetrazolyl group, an alkylcarbonylamino, alkylcarbonylaminomethyl,arylcarbonylamino, arylcarbonylaminomethyl, aralkylcarbonylamino,aralkylcarbonylaminomethyl, alkylsulphonylamino,alkylsulphonylaminomethyl, arylsulphonylamino, arylsulphonylaminomethyl,aralkylsulphonylamino, aralkylsulphonylaminomethyl,arylsulphonylaminocarbonyl or benzylsulphonylaminocarbonyl group, analkylsulphonylaminocarbonyl or perfluoroalkylsulphonylaminocarbonylgroup having in each case 1 to 6 carbon atoms in the alkyl moiety,

"a radical which can be converted in vivo to a group containing aBronsted acid", with the exception of the tert.-butoxycarbonyl group,especially means an alkoxycarbonyl group having a total of 2 to 7 carbonatoms, such as the methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl,isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl,n-pentoxycarbonyl or n-hexoxycarbonyl group, an aralkoxycarbonyl group,such as the benzyloxycarbonyl, 1-phenylethoxycarbonyl,2-phenylethoxycarbonyl or 3-phenylpropoxycarbonyl group or thepivaloyloxymethoxycarbonyl, phthalidylmethoxycarbonyl,ethoxycarbonyloxyethoxycarbonyl, methoxymethoxycarbonyl,cyclohexyloxycarbonylmethoxycarbonyl or(1,3-dioxa-2-oxo-4-methylcyclopenten-5-yl)-methoxycarbonyl group,

"an acyl group" especially means an alkanoyl group having 1 to 7 carbonatoms, a cycloalkylcarbonyl group

having a total of 4 to 8 carbon atoms, a cycloalkylalkanoyl group havinga total of 5 to 10 carbonatoms, or an arylcarbonyl, aralkanoyl orphenylsulphonyl group optionally substituted by a fluorine, chlorine orbromine atom or by an alkyl or alkoxy group,

"an aryl group" especially means a phenyl group optionally substitutedby a fluorine, chlorine or bromine atom, or by a hydroxy, alkyl, alkoxy,phenylalkoxy or trifluoromethyl group, wherein the alkyl moiety maycontain 1 to 4 carbon atoms in each case, or a naphthyl group, and

"a cycloalkyl group" especially means a cycloalkyl group having 3 to 7carbon atoms, which may be substituted by one or two alkyl groups,wherein, provided that nothing else has been mentioned, the alkyl andalkanoyl moieties mentioned in the definition of the radicals R₁ to R₃,and the alkyl moieties mentioned above may contain 1 to 3 carbon atomsin each case.

The novel compounds of the above formula I have valuable properties.Hence, the compounds of the formula I, in which R₄ denotes a groupcontaining a Bronsted acid or a radical which can be converted in vivoto a group containing a Bronsted acid, have valuable pharmacologicalproperties, in particular these compounds are angiotensin IIantagonists.

The remaining compounds of the formula I are valuable intermediates asthey can be converted chemically to one of the pharmacologically activecompounds of the formula I mentioned above.

The present invention thus also relates to novel medicaments whichcontain one of the above-mentioned pharmacologically active compounds ofthe formula I or a corresponding physiologically acceptable additionsalt, and are particularly suitable for the treatment of hypertonia andcardiac insufficiency, also for the treatment of ischaemic peripheralcirculatory disorders, myocardial ischaemia (Angina), for the preventionof cardiac insufficiency progression after myocardial infarction, forthe treatment of diabetic nephropathy, glaucoma, gastrointestinalillnesses and diseases of the bladder.

Suitable examples of the meanings mentioned in the definition of theradicals R₁, R₂, R₃ and R₄ are

for R₁ the meaning hydrogen, fluorine, chlorine or bromine atom, methyl,ethyl, n-propyl, isopropyl, n-butyl, hydroxymethyl, 2-hydroxyethyl,2-hydroxyisopropyl, 3-hydroxypropyl, methoxymethyl, 2-methoxyethyl,2-ethoxyethyl, 2-methoxyisopropyl, 2-n-propoxyethyl, aminomethyl,1-aminoethyl, 2-aminoethyl, 3-aminopropyl, methylaminomethyl,dimethylaminomethyl, ethylaminomethyl, diethylaminomethyl,N-methyl-isopropylaminomethyl, 2-methylaminoethyl, 2-dimethylaminoethyl,2-isopropylaminoethyl, 2-diisopropylaminoethyl, 3-methylaminopropyl,3-dimethylaminopropyl, acetaminomethyl, propionylaminomethyl,butanoylaminomethyl, pentanoylaminomethyl, benzoylaminomethyl,benzenesulphonylaminomethyl, 2-acetaminoethyl, 2-propionylaminoethyl,2-butanoylaminoethyl, 2-benzoylaminoethyl, 3-acetaminopropyl, methoxy,ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-hydroxyethoxy,2-hydroxyisopropoxy, 3-hydroxypropoxy, 2-methoxyethoxy, 2-ethoxyethoxy,2-methoxyisopropoxy, 3-methoxypropoxy, 3-n-propoxypropoxy,2-aminoethoxy, 2-methylaminoethoxy, 2-dimethylaminoethoxy,2-ethylaminoethoxy, 2-diethylaminoethoxy, 2-isopropylaminoethoxy,3-aminopropoxy, 3-methylaminopropoxy, 3-dimethylaminopropoxy,2-(imidazol-1-yl)-ethoxy, 2-(imidazol-2-yl)-ethoxy,2-(imidazol-4-yl)-ethoxy, 3-(imidazol-1-yl)-propoxy,3-(imidazol-2-yl)-propoxy, 3-(imidazol-4-yl)-propoxy, hydroxy,benzyloxy, 2-phenylethoxy, 3-phenylpropoxy, acetoxy, propionyloxy,n-butanoyloxy, n-pentanoyloxy, trifluoromethylsulphonyloxy,methylaminocarbonyloxy, ethylaminocarbonyloxy,isopropylaminocarbonyloxy, dimethylaminocarbonyloxy,diethylaminocarbonyloxy, di-n-propylaminocarbonyloxy,N-methyl-ethylaminocarbony-loxy, cyclopropylaminocarbonyloxy,cyclobutylaminocarbonyloxy, cyclopentylaminocarbonyloxy,cyclohexylaminocarbonyloxy, cycloheptylaminocarbonyloxy,cyclopropylmethylaminocarbonyloxy, cyclobutylmethylaminocarbonyloxy,cyclopentylmethylaminocarbonyloxy, cyclohexylmethylaminocarbonyloxy,cycloheptylmethylaminocarbonyloxy,(2-cyclopropylethyl)-aminocarbonyloxy,(2-cyclobutylethyl)-aminocarbonyloxy,(2-cyclopentylethyl)-aminocarbonyloxy,(2-cyclohexylethyl)-aminocarbonyloxy,(2-cycloheptylethyl)-aminocarbonyloxy,(3-cyclopropylpropyl)-aminocarbonyloxy,(3-cyclobutylpropyl)-aminocarbonyloxy,(3-cyclopentylpropyl)-aminocarbonyloxy,(3-cyclohexylpropyl)-aminocarbonyloxy,(3-cycloheptylpropyl)-aminocarbonyloxy, methoxycarbonyloxy,ethoxycarbonyloxy, n-propoxycarbonyloxy, isopropoxycarbonyloxy,cyclopropoxycarbonyl-oxy, cyclobutoxycarbonyloxy,cyclopentoxycarbonyloxy, cyclohexoxycarbonyloxy,cycloheptoxycarbonyloxy, cyclopropylmethoxycarbonyloxy,cyclobutylmethoxycarbonyloxy, cyclopentylmethoxycarbonyloxy,cyclohexylmethoxycarbonyloxy, cycloheptylmethoxycarbonyloxy,(2-cyclopropylethoxy)-carbonyloxy, (2-cyclobutylethoxy)-carbonyloxy,(2-cyclopentylethoxy)-carbonyloxy, (2-cyclohexylethoxy)-carbonyloxy,(2-cycloheptyleth-oxy)-carbonyloxy, (3-cyclopropylpropoxy)-carbonyloxy,(3-cyclobutylpropoxy)-carbonyloxy, (3-cyclopentylpro-poxy)-carbonyloxy,(3-cyclohexylpropoxy)-carbonyloxy, (3cycloheptylpropoxy)-carbonyloxy,phenyloxycarbonyl-oxy, benzyloxycarbonyloxy,(2-phenylethoxy)-carbonyloxy, trifluoromethyl, phenylaminocarbonyloxy,benzylaminocarbonyloxy, (2-phenylethyl)-aminocarbonyloxy, cyano, nitro,methylmercapto, ethylmercapto, n-propylmercapto, isopropylmercapto,methylsulphinyl, ethylsulphinyl, n-propylsulphinyl, isopropylsulphinyl,methylsulphonyl, ethylsulphonyl, n-propylsulphonyl, isopropylsulphonyl,phenylsulphonyl, fluorophenylsulphonyl, chlorophenylsulphonyl,bromophenylsulphonyl, methylphenylsulphonyl, ethylphenylsulphonyl,isopropylphenylsulphonyl, methoxyphenylsulphonyl, ethoxyphenylsulphonyl,n-propoxyphenylsulphonyl, aminosulphonyl, methylaminosulphonyl,ethylaminosulphonyl, n-propylaminosulphonyl, isopropylaminosulphonyl,dimethylaminosulphonyl, diethylaminosulphonyl,di-n-propylaminosulphonyl, N-methylethylaminosulphonyl,phenylaminosulphonly, fluorophenylaminosulphonyl,chlorophenylaminosulphonyl, bromophenylaminosulphonyl,methylphenylaminosulphonyl, ethylphenylaminosulphonyl,isopropylphenylaminosulphonyl, methoxyphenylaminosulphonyl,ethoxyphenylaminosulphonyl, n-propoxyphenylaminosulphonyl,acetaminosulphonyl, propionylaminosulphonyl, n-butanoylaminosulphonyl,benzoylaminosulphonyl, fluorobenzoylaminosulphonyl,chlorobenzoylaminosulphonyl, bromobenzoylaminosulphonyl,methylbenzoylaminosulphonyl, methoxybenzoylaminosulphonyl, acetyl,propionyl, n-butanoyl, n-pentanoyl, n-hexanoyl, n-heptanoyl,phenylacetyl, 2-phenylpropionyl, cyclopropylcarbonyl,cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl,cycloheptylcarbonyl, cyclopropylmethylcarbonyl,cyclobutylmethylcarbonyl, cyclopentylmethylcarbonyl,cyclohexylmethylcarbonyl, cycloheptylmethylcarbonyl,(2-cyclopropylethyl)-carbonyl, (2-cyclobutylethyl)-carbonyl,(2-cyclopentylethyl)-carbonyl, (2-cyclohexylethyl)-carbonyl,(2-cycloheptylethyl)-carbonyl,(3-cyclopropylpropyl)-carbonyl,(3-cyclobutylpropyl)-carbonyl,(3-cyclopentylpropyl)-carbonyl, (3-cyclohexylpropyl)-carbonyl,(3-cycloheptylpropyl)-carbonyl, benzoyl, fluorobenzoyl, chlorobenzoyl,bromobenzoyl, methylbenzoyl, methoxybenzoyl, phenylsulphonyl,fluorophenylsulphonyl, chlorophenylsulphonyl, bromophenylsulphonyl,methylphenylsulphonyl, methoxyphenylsulphonyl, amino,2-(imidazol-1-yl)-ethylamino, 2-(imidazol-1-yl)-isopropylamino,3-(imidazol-1-yl)-propylamino, (imidazol-4-yl)-methylamino,2-(imidazol-4-yl)-ethylamino, 2-(imidazo-4-yl)-isopropylamino,3-(imidazol-4-yl)-propylamino, acetylamino, propionylamino,n-butanoylamino, isobutanoylamino, n-pentanoylamino, n-hexanoylamino,n-heptanoylamino, cyclopropylcarbonylamino, cyclobutylcarbonylamino,cyclopentylcarbonylamino, cyclohexylcarbonylamino,cycloheptylcarbonylamino, cyclopropylmethylcarbonylamino,cyclobutylmethylcarbonylamino, cyclopentylmethylcarbonylamino,cyclohexylmethylcarbonylamino, cycloheptylmethylcarbonylamino,(2-cyclopropylethyl)-carbonylamino, (2-cyclobutylethyl)-carbonylamino,(2-cyclopentylethyl)-carbonylamino, (2-cyclohexyl-ethyl)-carbonylamino,(2-cycloheptylethyl)-carbonyl-amino,(3-cyclopropylpropyl)-carbonylamino, (3-cyclobutylpropyl)-carbonylamino,(3-cyclopentylpropyl)-carbonylamino, (3-cyclohexylpropyl)-carbonylamino,(3-cycloheptylpropyl)-carbonylamino, benzoylamino, fluorobenzoylamino,chlorobenzoylamino, bromobenzoyl-amino, methylbenzoylamino,hydroxybenzoylamino, methoxybenzoylamino, phenylacetylamino,phenylpropionylamino, naphthylcarbonylamino, methoxycarbonylamino,ethoxycarbonylamino, n-propoxycarbonylamino,cyclopropyloxycarbonylamino, cyclobutyloxycarbonylamino,cyclopentoxycarbonylamino, cyclohexoxycarbonylamino,cycloheptoxycarbonylamino, cyclopropylmethoxycarbonylamino,cyclobutylmethoxycarbonylamino, cyclopentylmethoxycarbonylamino,cyclohexylmethoxycarbonylamino, cycloheptylmethoxycarbonylamino,(2-cyclopropylethoxy)-carbonylamino, (2-cyclobutylethoxy)-carbonylamino,(2-cyclopentylethoxy)-carbonylamino, (2-cyclohexylethoxy)-carbonylamino,(2-cycloheptylethoxy)-carbonylamino,(3-cyclopropylpropoxy)-carbonylamino,(3-cyclobutylpropoxy)-carbonylamino,(3-cyclopentylpropoxy)-carbonylamino,(3-cyclohexylpropoxy)-carbonylamino,(3-cycloheptylpropoxy)-carbonylamino, phenoxycarbonylamino,fluorophenoxycarbonylamino, chlorophenoxycarbonylamino,bromophenoxycarbonylamino, methylphenoxycarbonylamino,hydroxyphenoxycarbonylamino, methoxyphenoxycarbonylamino,benzyloxyphenoxycarbonylamino, benzyloxycarbonylamino,(2-phenylethoxy)-carbonylamino, trifluoroacetylamino, decalinylamino,adamantylamino, methylsulphonylamino, ethylsulphonylamino,n-propylsulphonylamino, n-butylsulphonylamino, methylamino, ethylamino,n-propylamino, isopropylamino, n-butylamino, isobutylamino,n-pentylamino, n-hexylamino, dimethylamino, diethylamino,di-n-propylamino, methyl-ethylamino, methyl-isopropylamino,methyl-n-butylamino, ethyl-n-propylamino,N-n-propylsulphonyl-methylamino, methyl-n-pentylamino,ethyl-n-hexylamino, N-methylsulphonyl-methylamino,N-ethylsulphonyl-methylamino, N-n-propylsulphonyl-methylamino,N-methylsulphonyl-ethylamino, N-ethylsulphonyl-ethylamino,N-n-propylsulphonyl-ethylamino, N-methylsulphonyl-n-propylamino,N-ethylsulphonyl-n-propylamino, N-n-propylsulphonyl-n-propylamino,N-methylsulphonyl-n-butylamino, N-ethylsulphonyl-n-pentylamino,N-n-propylsulphonyl-n-hexylamino, N-acetyl-methylamino,N-acetyl-ethylamino, N-acetyl-n-hexylamino, N-propionyl-methylamino,N-propionyl-ethyl-amino, N-propionyl-n-butylamino,N-n-butanoyl-methyl-amino, N-n-butanoyl-ethylamino,N-n-butanoyl-n-pentyl-amino, N-isobutanoyl-methylamino,N-isobutanoyl-ethyl-amino, N-isobutanoyl-isopropylamino,N-isobutanoyl-n-pentylamino, N-n-pentanoyl-methylamino,N-n-pentanoyl-ethylamino, N-n-pentanoyl-isopropylamino,N-n-pentanoyl-n-pentylamino, N-n-hexanoyl-methylamino,N-n-hexanoyl-ethylamino, N-n-hexanoyl-isopropylamino,N-n-hexanoyl-n-pentylamino, N-n-heptanoyl-methylamino,N-n-heptanoyl-ethylamino, N-n-heptanoyl-isopropylamino,N-n-heptanoyl-n-pentylamino, N-cyclopropyl-carbonylmethyl-amino,N-cyclobutylcarbonyl-methylamino, N-cyclopentylcarbonyl-methylamino,N-cyclohexylcarbonyl-methylamino, N-cycloheptylcarbonyl-methylamino,N-cyclopropylmethylcarbonyl-methylamino,N-cyclobutylmethylcarbonyl-methylamino,N-cyclopentyl-methylcarbonyl-methylamino,N-cyclohexylmethylcarbonyl-methylamino,N-cycloheptylmethylcarbonyl-methylamino,N-(2-cyclopropylethylcarbonyl)-methylamino,N-(2-cyclobutylethylcarbonyl)-methylamino,N-(2-cyclopentylethylcarbonyl)-methylamino,N-(2-cyclohexylethylcarbonyl)-methylamino,N-(2-cycloheptylethylcarbonyl)-methylamino,N-(3-cyclopropylpropyl-carbonyl)-methylamino,N-(3-cyclobutylpropyl-carbonyl)-methylamino,N-(3-cyclopentylpropyl-carbonyl)-methylamino,N-(3-cyclohexylpropyl-carbonyl)-methylamino,N-(3-cycloheptylpropyl-carbonyl)-methylamino, N-benzoyl-methylamino,N-benzoyl-ethylamino, N-benzoyl-isopropylamino, N-benzoyl-n-butylamino,N-benzoyl-n-pentylamino, N-benzoyl-n-hexylamino,N-fluorobenzoyl-methylamino, N-methylbenzoyl-ethylamino,N-methoxybenzoyl-isopropylamino, N-chlorobenzoyl-n-butylamino,N-fluorobenzoyl-n-pentylamino, N-bromobenzoyl-n-hexylamino,N-phenylacetyl-methylamino, N-phenyl-sulphonyl-methylamino,N-(2-hydroxyethyl)-methyl-amino, N-(2-hydroxyethyl)-ethyl-amino,N-(2-methoxyethyl)-methylamino, N-(2-methoxy-ethyl)-ethylamino,N-hydroxy-acetyl-methylamino, N-hydroxyacetyl-ethylamino,N-methoxyacetyl-methylamino, N-methoxyacetyl-ethylamino,cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino,cycloheptylamino, cyclopropylmethylamino, cyclobutylmethyl-amino,cyclopentylmethylamino, cyclohexylmethylamino, cycloheptylmethylamino,(2-cyclopropylethyl)-amino, (2-cyclobutylethyl)-amino,(2-cyclopentylethyl)-amino, (2-cyclohexylethyl)-amino,(2-cycloheptylethyl)-amino, (3-cyclopropylpropyl)-amino,(3-cyclopentylpropyl)-amino, (3-cyclohexylpropyl)-amino,(3-cycloheptyl-propyl)-amino, benzylamino, 2-phenylethyl-amino,3-phenylpropylamino, phenylamino, dicyclohexyl-amino,dicyclohexylmethylamino, dibenzylamino, N-methyl-cyclopropylamino,N-isopropyl-cyclopropylamino, N-ethyl-cyclobutylamino,N-methyl-cyclopentylamino, N-ethyl-cyclohexylamino,N-(n-propyl)-cycloheptylamino, N-methyl-cyclopropylmethylamino,N-isopropyl-cyclopropylmethylamino, N-ethyl-cyclobutylmethylamino,N-methyl-cyclopentylmethylamino, N-ethyl-cyclohexyl-methylamino,N-(n-propyl)-cycloheptylmethylamino,N-methyl-(2-cyclopropylethyl)-amino,N-isopropyl-(2-cyclopropylethyl)-amino,N-ethyl-(2-cyclobutylethyl)-amino, N-methyl-(2-cyclopentylethyl)-amino,N-ethyl-(2-cyclohexylethyl)-amino,N-(n-propyl-(2-cycloheptyl-ethyl)-amino,N-methyl-(3-cyclopropylpropyl)-amino,N-isopropyl-(3-cyclopropylpropyl)-amino,N-ethyl-(3-cyclobutylpropyl)-amino,N-methyl-(3-cyclopentylpropyl)-amino,N-ethyl-(3-cyclohexylpropyl)-amino,N-(n-propyl)-(3-cycloheptylpropyl)-amino, N-methyl-benzyl-amino,N-ethyl-benzylamino, N-isopropyl-benzylamino,N-methyl-(2-phenylethyl)-amino, N-methyl-phenylamino,N-(n-propyl)-phenylamino, pyrrolidino, methyl-pyrrolidino,ethylpyrrolidino, isopropylpyrroli-dino, cyclopentylpyrrolidino,cyclohexylpyrrolidino, cycloheptylpyrrolidino, phenylpyrrolidino,piperidino, methylpiperidino, ethylpiperidino, isopropylpiperidino,cyclopentylpiperidino, cyclohexylpiperidino, cycloheptylpiperidino,phenylpiperidino, hexamethyleneimino, methylhexamethyleneimino,ethylhexamethyleneimino, isopropylhexamethyleneimino,cyclopentylhexamethyleneimino, cyclohexylhexamethyleneimino,cycloheptylhexamethyleneimino, phenylhexamethyleneimino,N-methoxycarbonyl-methylamino, N-methoxycarbonyl-N-ethylamino,N-methoxycarbonyl-n-pentylamino, N-methoxycarbonyl-n-hexylamino,N-ethoxycarbonyl-methylamino, N-ethoxycarbonyl-ethylamino,N-cyclopropyloxycarbonyl-methylamino,N-cyclopropyloxycarbonyl-ethylamino,N-cyclopropyloxycarbonyl-n-propylamino,N-cyclobutyloxycarbonyl-methylamino,N-cyclobutyloxycarbonyl-isopropylamino,N-cyclopentyloxycarbonyl-methylamino,N-cyclopentyloxycarbonyl-ethylamino,N-cyclohexyloxy-carbonyl-methylamino,N-cyclohexyloxycarbonyl-ethylamino,N-cycloheptyloxycarbonyl-methylamino,N-cyclopentylmethyloxycarbonyl-methylamino,N-cyclopentylmethyloxycarbonyl-ethylamino,N-cyclohexylmethyloxycarbonyl-methylamino,N-cyclohexylmethyloxycarbonyl-ethylamino,N-cycloheptylmethyloxycarbonyl-methylamino,N-cycloheptylmethyloxycarbonyl-ethylamino,N-(2-cyclopentylethyloxy)-carbonyl-methylamino,N-(2-cyclopentylethyloxy)-carbonyl-ethylamino,N-(2-cyclohexylethyloxy)-carbonyl-methylamino,N-(2-cyclohexylethyloxy)-carbonyl-ethylamino,N-(2-cycloheptylethyloxy)-carbonyl-methylamino,N-(2-cycloheptylethyloxy)-carbonyl-ethylamino,N-phenoxycarbonyl-methylamino, N-phenoxycarbonyl-ethylamino,N-phenoxycarbonyl-isopropylamino, N-benzyloxycarbonyl-methylamino,N-benzyloxycarbonyl-ethylamino, N-benzyloxycarbonyl-isopropylamino,N-(2-phenylethoxy)-carbonyl-methylamino,N-(2-phenylethoxy)-carbonyl-ethylamino,N-(2-phenylethoxy)-carbonyl-isopropylamino,N-(3-phenylpropoxy)-carbonyl-methylamino,N-(3-phenylpropoxy)-carbonyl-ethylamino,N-(3-phenylpropoxy)-carbonyl-isopropylamino,N-methoxycarbonyl-cyclopropylamino, N-methoxycarbonyl-cyclobutylamino,N-methoxycarbonyl, cyclopentylamino, N-methoxycarbonyl-cyclohexylamino,N-methoxycarbonyl-cycloheptylamino, N-ethoxycarbonyl-cyclopropylamino,N-ethoxycarbonyl-cyclobutylamino, N-ethoxycarbonyl-cyclopentylamino,N-ethoxycarbonyl-cyclohexylamino, N-ethoxycarbonyl-cycloheptylamino,N-methoxycarbonyl-cyclopropylmethylamino,N-methoxycarbonyl-cyclobutylmethylamino,N-methoxycarbonyl-cyclopentylmethylamino,N-methoxycarbonyl-cyclohexylmethylamino,N-methoxycarbonyl-cycloheptylmethylamino,N-ethoxycarbonyl-cyclopropylmethylamino,N-ethoxycarbonyl-cyclobutylmethylamino,N-ethoxycarbonyl-cyclopentylmethylamino,N-ethoxycarbonyl-cyclohexylmethylamino,N-ethoxycarbonyl-cycloheptylmethylamino,N-methoxycarbonyl-(2-cyclopropylethyl)-amino,N-methoxycarbonyl-(2-cyclobutylethyl)-amino,N-methoxycarbonyl-(2-cyclopentylethyl-amino,N-methoxycarbonyl-(2-cyclohexylethyl-amino,N-methoxycarbonyl-(2-cycloheptylethyl)-amino,N-ethoxycarbonyl-(2-cyclopropylethyl)-amino,N-ethoxycarbonyl-(2-cyclobutylethyl-amino,N-ethoxycarbonyl-2-cyclopentylethyl)-amino,N-ethoxycarbonyl-(2-cyclohexylethyl)-amino,N-ethoxycarbonyl-(2-cycloheptylethyl)-amino,N-methoxycarbonyl-(3-cyclopropylpropyl)-amino,N-methoxycarbonyl-(3-cyclobutylpropyl)-amino,N-methoxycarbonyl-(3-cyclopentylpropyl)-amino,N-methoxycarbonyl-(3-cyclohexylpropyl)-amino,N-methoxycarbonyl-(3-cycloheptylpropyl)-amino,N-ethoxycarbonyl-(3-cyclopropylpropyl)-amino,N-ethoxycarbonyl-(3-cyclobutylpropyl)-amino,N-ethoxycarbonyl-(3-cyclopentylpropyl)-amino,N-ethoxycarbonyl-(3-cyclohexylpropyl)-amino,N-ethoxycarbonyl-(3-cycloheptylpropyl)-amino,N-phenoxycarbonyl-cyclopropylamino, N-phenoxycarbonyl-cyclobutylamino,N-phenoxycarbonyl-cyclopentylamino, N-phenoxycarbonyl-cyclohexylamino,N-phenoxycarbonyl-cycloheptylamino,N-benzyloxycarbonyl-cyclopropylamino,N-benzyloxycarbonyl-cyclobutylamino,N-benzyloxycarbonyl-cyclopentylamino,N-benzyloxycarbonyl-cyclohexylamino,N-benzyloxycarbonyl-cycloheptylamino,N-(2-phenylethoxy)-carbonyl-cyclopropylamino,N-(2-phenylethoxy)-carbonyl-cyclobutylamino,N-(2-phenylethoxy)-carbonyl-cyclopentylamino,N-(2-phenylethoxy)-carbonyl-cyclohexylamino,N-(2-phenylethoxy)-carbonyl-cycloheptylamino,N-(3-phenylpropoxy)-carbonyl-cyclopropylamino,N-(3-phenylpropoxy)-carbonyl-cyclobutylamino,N-(3-phenylpropoxy)-carbonyl-cyclopentylamino,N-(3-phenylpropoxy)-carbonyl-cyclohexylamino,N-(3-phenylpropoxy)-carbonyl-cycloheptylamino,N-methylsulphonyl-cyclopropylamino, N-ethylsulphonyl-cyclobutylamino,N-n-propylsulphonyl-cyclopentylamino, N-ethylsulphonyl-cyclohexylamino,N-methylsulphonyl-cycloheptylamino,N-phenoxycarbonyl-cyclopropylmethylamino,N-phenoxycarbonyl-cyclobutylmethylamino,N-phenoxycarbonyl-cyclopentylmethylamino,N-phenoxycarbonyl-cyclohexylmethylamino,N-phenoxycarbonyl-cycloheptylmethylamino,N-benzyloxycarbonyl-cyclopropylmethylamino,N-benzyloxycarbonyl-cyclobutylmethylamino,N-benzyloxycarbonyl-cyclopentylmethylamino,N-benzyloxycarbonyl-cyclohexylmethylamino,N-benzyloxycarbonyl-cycloheptylmethylamino,N-(2-phenylethoxycarbonyl)-cyclopropylmethylamino,N-(2-phenylethoxycarbonyl)-cyclobutylmethylamino,N-(2-phenylethoxycarbonyl-cyclopentylmethylamino,N-(2-phenylethoxycarbonyl-cyclohexylmethylamino,N-(2-phenylethoxycarbonyl-cycloheptylmethylamino,N-(3-phenylpropoxycarbonyl-cyclopropylmethylamino,N-(3-phenylpropoxycarbonyl)-cyclobutylmethylamino,N-(3-phenylpropoxycarbonyl)-cyclopentylmethylamino,N-(3-phenylpropoxycarbonyl)-cyclohexylmethylamino,N-(3-phenylpropoxycarbonyl)-cycloheptylmethylamino,N-methylsulphonyl-cyclopropylmethylamino,N-ethylsulphonyl-cyclobutylmethylamino,N-methylsulphonyl-cyclopentylmethylamino,N-ethylsulphonyl-cyclohexylmethylamino,N-ethylsulphonyl-cyclohexylmethylamino,N-isopropylsulphonyl-cycloheptylmethylamino,N-phenoxycarbonyl-(2-cyclopropylethyl)-amino,N-phenoxycarbonyl-(2-cyclobutylethyl)-amino,N-phenoxycarbonyl-(2-cyclopentylethyl)-amino,N-phenoxycarbonyl-(2-cyclohexylethyl)-amino,N-phenoxycarbonyl-(2-cycloheptylethyl)-amino,N-benzyloxycarbonyl-(2-cyclopropylethyl)-amino,N-benzyloxycarbonyl-(2-cyclobutylethyl)-amino,N-benzyloxycarbonyl-(2-cyclopentylethyl)-amino,N-benzyloxycarbonyl-(2-cyclohexylethyl)-amino,N-benzyloxycarbonyl-(2-cycloheptylethyl)-amino,N-(2-phenylethoxycarbonyl)-2-cyclopropylethyl)-amino,N-(2-phenylethoxycarbonyl)-(2-cyclobutylethyl)-amino,N-(2-phenylethoxycarbonyl)-(2-cyclopentylethyl)-amino,N-(2-phenylethoxycarbonyl)-2-cyclohexylethyl)-amino,N-(2-phenylethoxycarbonyl)-(2-cycloheptylethyl)-amino,N-(3-phenylpropoxycarbonyl)-(2-cyclopropylethyl)-amino,N-(3-phenylpropoxycarbonyl)-(2-cyclobutylethyl)-amino,N-(3-phenylpropoxycarbonyl)-2-cyclopentylethyl)-amino,N-(3-phenylpropoxycarbonyl)-(2-cyclohexylethyl)-amino,N-(3-phenylpropoxycarbonyl)-(2-cycloheptylethyl)-amino,N-methylsulphonyl-(2-cyclopropylethyl)-amino,N-ethylsulphonyl-(2-cyclobutylethyl)-amino,N-isopropylsulphonyl-(2-cyclopentylethyl)-amino,N-methylsulphonyl-(2-cyclohexylethyl)-amino,N-methylsulphonyl-(2-cycloheptylethyl)-amino,N-phenoxycarbonyl-(3-cyclopropylpropyl)-amino,N-phenoxycarbonyl-(3-cyclobutylpropyl)-amino,N-phenoxycarbonyl-(3-cyclopentylpropyl)-amino,N-phenoxycarbonyl-(3-cyclohexylpropyl)-amino,N-phenoxycarbonyl-(3-cycloheptylpropyl)-amino,N-benzyloxycarbonyl-(3-cyclopropylpropyl)-amino,N-benzyloxycarbonyl-(3-cyclobutylpropyl)-amino,N-benzyloxycarbonyl-(3-cyclopentylpropyl)-amino,N-benzyloxycarbonyl-(3-cyclohexylpropyl)-amino,N-benzyloxycarbonyl-(3-cycloheptylpropyl)-amino,N-(2-phenylethoxycarbonyl)-(3-cyclopropylpropyl)-amino,N-(2-phenylethoxycarbonyl)-(3-cyclobutylpropyl)-amino,N-(2-phenylethoxycarbonyl)-(3-cyclopentylpropyl)-amino,N-(2-phenylethoxycarbonyl)-(3-cyclohexylpropyl)-amino,N-(2-phenylethoxycarbonyl)-(3-cycloheptylpropyl)-amino,N-(3-phenylpropoxycarbonyl)-(3-cyclopropylpropyl)-amino,N-(3-phenylpropoxycarbonyl)-(3-cyclobutylpropyl)-amino,N-(3-phenylpropoxycarbonyl)-(3-cyclopentylpropyl)-amino,N-(3-phenylpropoxycarbonyl)-(3-cyclohexylpropyl)-amino,N-(3-phenylpropoxycarbonyl)-(3-cycloheptylpropyl)-amino,N-methylsulphonyl-(3-cyclopropylpropyl)-amino,N-ethylsulphonyl-(3-cyclobutylpropyl)-amino,N-isopropylsulphonyl-(3-cyclopentylpropyl)-amino,N-methylsulphonyl-(3-cyclohexylpropyl)-amino,N-methylsulphonyl-(3-cycloheptylpropyl)-amino,N-benzoyl-cyclopropylamino, N-benzoyl-cyclobutylamino,N-benzoyl-cyclopentylamino, N-benzoyl-cyclohexylamino,N-benzoyl-cycloheptylamino, N-phenylacetyl-cyclopropylamino,N-phenylacetyl-cyclobutylamino, N-phenylacetyl-cyclopentylamino,N-phenylacetyl-cyclohexylamino, N-phenylacetyl-cycloheptylamino,N-phenylsulphonyl-cyclopropylamino, N-phenylsulphonyl-cyclobutylamino,N-phenylsulphonyl-cyclopentylamino, N-phenylsulphonyl-cyclohexylamino,N-phenylsulphonyl-cycloheptylamino, N-benzoyl-cyclopropylmethylamino,N-benzoyl-cyclobutylmethylamino, N-benzoyl-cyclopentylmethylamino,N-benzoyl-cyclohexylmethylamino, N-benzoyl-cycloheptylmethylamino,N-phenylacetyl-cyclopropylmethylamino,N-phenylacetyl-cyclobutylmethylamino,N-phenylacetyl-cyclopentylmethylamino,N-phenylacetyl-cyclohexylmethylamino,N-phenylacetyl-cycloheptylmethylamino,N-phenylsulphonyl-cyclopropylmethylamino,N-phenylsulphonyl-cyclobutylmethylamino,N-phenylsulphonyl-cyclopentylmethylamino,N-phenyl-sulphonyl-cyclohexylmethylamino,N-phenylsulphonyl-cycloheptylmethylamino,N-benzoyl-(2-cyclopropyl-ethyl)-amino,N-benzoyl-(2-cyclobutylethyl)-amino,N-benzoyl-(2-cyclopentylethyl)-amino,N-benzoyl-(2-cyclohexylethyl)-amino,N-benzoyl-(2-cycloheptyl-ethyl)-amino,N-phenylacetyl-(2-cyclopropylethyl)-amino,N-phenylacetyl-(2-cyclobutylethyl)-amino,N-phenyl-acetyl-(2-cyclopentylethyl)-amino,N-phenylacetyl-(2-cyclohexylethyl)-amino,N-phenylacetyl-(2-cycloheptylethyl)-amino,N-phenylsulphonyl-(2-cyclopropylethyl)-amino,N-phenylsulphonyl-(2-cyclobutylethyl)-amino,N-phenylsulphonyl-(2-cyclopentylethyl)-amino,N-phenylsulphonyl-(2-cyclohexylethyl)-amino,N-phenylsulphonyl-(2-cycloheptylethyl)-amino,N-benzoyl-(3-cyclopropylpropyl)-amino,N-benzoyl-(3-cyclobutylpropyl)-amino,N-benzoyl-(3-cyclopentylpropyl)-amino,N-benzoyl-(3-cyclohexylpropyl)-amino,N-benzoyl-(3-cycloheptylpropyl)-amino,N-phenylacetyl-(3-cyclopropylpropyl)-amino,N-phenylacetyl-(3-cyclobutylpropyl)-amino,N-phenylacetyl-(3-cyclopentylpropyl)-amino,N-phenylacetyl-(3-cyclohexylpropyl)-amino,N-phenylacetyl-(3-cycloheptylpropyl)-amino,N-phenylsulphonyl-(3-cyclopropylpropyl)-amino,N-phenylsulphonyl-(3-cyclobutylpropyl)-amino,N-phenylsulphonyl-(3-cyclopentylpropyl)-amino,N-phenylsulphonyl-(3cyclohexylpropyl)-amino,N-phenylsulphonyl-(3-cycloheptylpropyl)-amino,N-acetyl-cyclopropylamino, N-acetyl-cyclobutylamino,N-acetyl-cyclopentylamino, N-acetyl-cyclohexylamino,N-acetyl-cycloheptylamino, N-acetyl-cyclopropylmethylamino,N-acetyl-cyclobutylmethylamino, N-acetyl-cyclopentylmethylamino,N-acetyl-cyclohexylmethylamino, N-acetyl-cycloheptylmethylamino,N-acetyl-(2-cyclopropylethyl)-amino, N-acetyl-(2-cyclobutylethyl)-amino,N-acetyl-(2-cyclopentylethyl)-amino, N-acetyl-(2-cyclohexylethyl)-amino,N-acetyl-(2-cycloheptylethyl)-amino,N-acetyl-(3-cyclopropylpropyl)-amino,N-acetyl-(3-cyclobutylpropyl)-amino,N-acetyl-(3-cyclopentyl-propyl)-amino,N-acetyl-(3-cyclohexylpropyl)-amino,N-acetyl-(3-cycloheptylpropyl)-amino, N-acetyl-benzyl-amino,N-acetyl-(2-phenylethyl)-amino, N-acetyl-(3-phenylpropyl)-amino,N-benzoyl-benzylamino, N-benzoyl-(2-phenylethyl)-amino,N-benzoyl-(3-phenyl-propyl)-amino, N-methylsulphonyl-benzylamino,N-methyl-sulphonyl-(2-phenylethyl)-amino,N-methylsulphonyl-(3-phenylpropyl)-amino, carboxy, methoxycarbonyl,ethoxycarbonyl, n-propoxycarbonyl, aminocarbonyl, methylaminocarbonyl,ethylaminocarbonyl, n-propylaminocarbonyl, n-butylaminocarbonyl,n-pentylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl,diisopropylaminocarbonyl, cyclopropylaminocarbonyl,cyclobutylaminocarbonyl, cyclopentylaminocarbonyl,cyclohexylaminocarbonyl, cycloheptylaminocarbonyl,cyclopentylmethylaminocarbonyl, cyclohexylmethylaminocarbonyl,cycloheptylmethylaminocarbonyl, 2-cyclohexylethyl-aminocarbonyl,phenylaminocarbonyl, fluorophenylaminocarbonyl,chlorophenylaminocarbonyl, bromophenylaminocarbonyl,methylphenylaminocarbonyl, ethylphenylaminocarbonyl,isopropylphenylaminocarbonyl, methoxyphenylaminocarbonyl,ethoxyphenylaminocarbonyl, isopropoxyphenylaminocarbonyl,n-butoxyphenylaminocarbonyl, benzylaminocarbonyl,(2-phenylethyl)-aminocarbonyl, dimethylaminocarbonyl,diethylaminocarbonyl, diisopropylaminocarbonyl,N-methylethylaminocarbonyl, N-methyl-n-propylaminocarbonyl,N-methyl-n-butylaminocarbonyl, aminoacetylamino,N-methoxycarbonyl-amino-acetylamino, N-ethoxycarbonyl-aminoacetylamino,N-isopropoxycarbonyl-aminoacetylamino, aminocarbonylamino,methylaminocarbonylamino, dimethylaminocarbonylamino,N-methylaminocarbonyl-methylamino,N-(dimethylaminocarbonyl)-methylamino,N-dimethylaminocarbonylethylamino,N-dimethylaminocarbonyl-isopropylamino,N-(dimethylaminocarbonyl)-n-pentylamino,N-methylaminocarbonyl-ethylamino, N-methylaminocarbonyl-n-pentylamino,N-methylaminocarbonyl-n-hexylamino, N-methylaminocarbonyl-n-octylamino,N-methylaminocarbonyl-n-dodecylamino,N-methylaminocarbonyl-cyclohexylamino, ethylaminocarbonylamino,N-ethylaminocarbonylmethylamino, N-ethylaminocarbonyl-ethylamino,N-ethylaminocarbonyl-n-hexylamino, N-ethylaminocarbonyl-n-octylamino,N-ethylaminocarbonyl-n-dodecylamino,N-ethylaminocarbonyl-cyclohexylamino, diethylaminocarbonylamino,N-(diethylaminocarbonyl)-methylamino,N-(diethylaminocarbonyl)-ethylamino,N-(diethylaminocarbonyl)-n-butylamino,N-(diethylaminocarbonyl)-n-hexylamino,N-(diethylaminocarbonyl)-n-octylamino,N-(diethylaminocarbonyl)-n-dodecylamino, isopropylaminocarbonylamino,N-isopropylaminocarbonyl-methylamino, n-butylaminocarbonylamino,N-(n-butylaminocarbonyl)-methylamino,N-(n-butylaminocarbonyl)-ethyl-amino,N-(n-butylaminocarbonyl)-isopropylamino,N-(n-butylaminocarbonyl)-n-butylamino,N-(n-butylaminocarbonyl)-n-hexylamino,N-(n-butylaminocarbonyl)-n-octylamino,N-(n-butylaminocarbonyl)-n-dodecylamino,N-(n-butylaminocarbonyl)-cyclohexylamino,N-(di-(n-butyl)-aminocarbonyl)-amino,N-(di-(n-butyl)-aminocarbonyl)-methylamino,N-(di-(n-butyl)-aminocarbonyl)-ethylamino,N-(di-(n-butyl)-aminocarbonyl)-n-butylamino,N-(di-(n-butyl)-aminocarbonyl)-n-hexylamino,N-(di-(n-butyl)-aminocarbonyl-n-octylamino,N-(di-(n-butyl)-aminocarbonyl)-n-dodecylamino,N-(n-pentylaminocarbonyl)-ethylamino,N-(n-hexylaminocarbonyl)-ethylamino,N-(n-octylaminocarbonyl)-ethylamino,N-(n-dodecylaminocarbonyl)-ethylamino, n-hexylamino-carbonylamino,n-octylaminocarbonylamino, n-dodecylaminocarbonylamino,N-(n-hexylaminocarbonyl)-n-butylamino,N-(n-hexylaminocarbonyl)-n-pentylamino,N-(n-hexylaminocarbonyl)-n-hexylamino,N-(n-hexyl-aminocarbonyl)-n-octylamino,N-(n-hexylaminocarbonyl)-n-dodecylamino,N-(n-octylaminocarbonyl)-n-butylamino,N-(n-octylaminocarbonyl)-n-pentylamino,N-(n-octyl-aminocarbonyl)-n-hexylamino,N-(n-octylaminocarbonyl)-n-octylamino,N-(n-octylaminocarbonyl)-n-dodecylamino,N-(n-dodecylaminocarbonyl)-n-butylamino,N-(n-dodecylaminocarbonyl)-n-pentylamino,N-(n-dodecylaminocarbonyl)-n-hexylamino,N-(n-dodecylaminocarbonyl)-n-octylamino,N-(n-dodecylaminocarbonyl)-n-dodecylamino,N-(n-hexylaminocarbonyl)-cyclohexylamino,N-(n-octylaminocarbonyl)-cyclohexylamino,N-(n-dodecylaminocarbonyl)-cyclohexylamino,di-(n-hexyl)-aminocarbonylamino,N-(di-(n-hexyl)-aminocarbonyl)-methylamino,N-(methyl-(n-hexyl)-aminocarbonyl)-amino,N-cyclohexylaminocarbonyl-n-pentylamino,N-cyclohexylaminocarbonyl-n-hexylamino,N-cyclohexylaminocarbonyl-n-octylamino,N-cyclohexylaminocarbonyl-n-dodecylamino,N-cyclohexylaminocarbonyl-cyclohexylamino,N-(ethyl-cyclohexylaminocarbonyl)-methylamino,N-(propyl-cyclohexylaminocarbonyl)-methylamino,N-(n-butyl-cyclohexylaminocarbonyl)-methylamino,adamant-1-yl-aminocarbonylamino, 4-hydroxybutylaminocarbonylamino,5-hydroxypentylaminocarbonylamino, 6-hydroxyhexylaminocarbonylamino,allyl-aminocarbonylamino, but-2-enylaminocarbonylamino,pent-2-enylaminocarbonylamino, pent-3-enylaminocarbonylamino,crotylaminocarbonylamino, but-2-ynylaminocarbonylamino,pent-2-ynylaminocarbonylamino, pent-3-ynylaminocarbonylamino,tetrahydrofuran-2-yl-aminocarbonylamino,tetrahydropyran-2-yl-aminocarbonylamino,N-(ethyl-(n-pentyl)-aminocarbonyl)-ethylamino,N-(methyl-cyclopentylaminocarbonyl)-methylamino,N-(methyl-cyclohexylaminocarbonyl)-ethylamino,cyclopropylaminocarbonylamino, N-cyclopropylaminocarbonyl-methylamino,cyclobutylaminocarbonylamino, N-cyclobutylaminocarbonyl-methylamino,cyclopentylaminocarbonylamino, N-cyclopentylaminocarbonyl-methylamino,cyclohexylaminocarbonylamino, N-cyclohexylaminocarbonyl-methylamino,N-cyclohexylaminocarbonyl-ethylamino,N-cyclohexylaminocarbonyl-n-propylamino,N-cyclohexylaminocarbonyl-n-butylamino,N-cyclohexylaminocarbonyl-n-pentylamino,N-cyclohexylaminocarbonyl-n-hexylamino,N-cyclohexylaminocarbonyl-n-octylamino,N-cyclohexylaminocarbonyl-n-dodecylamino, cycloheptylaminocarbonylamino,N-cycloheptylaminocarbonyl-methylamino,cyclopentylmethylaminocarbonylamino,N-cyclopentylmethylamincarbonyl-methylamino,cyclohexylmethylaminocarbonylamino,N-cyclohexylmethylaminocarbonyl-methylamino, benzylaminocarbonylamino,(2-phenylethyl)-aminocarbonylamino, phenylaminocarbonylamino,fluorophenylaminocarbonylamino, chlorophenylaminocarbonylamino,bromophenylaminocarbonylamino, methylphenylaminocarbonylamino,ethylphenylaminocarbonylamino, isopropylphenylaminocarbonylamino,methoxyphenylaminocarbonylamino, ethoxyphenylaminocarbonylamino,isopropoxyphenylaminocarbonylamino, n-butoxyphenylaminocarbonylamino,aminothiocarbonylamino, methylaminothiocarbonylamino,N-methylaminocarbonylmethylamino, N-methylaminocarbonyl-ethylamino,ethylaminothiocarbonylamino, N-ethylaminothiocarbonylmethylamino,N-ethylaminothiocarbonyl-ethylamino,N-ethylaminothiocarbonyl-n-hexylamino, isopropylaminothiocarbonylamino,N-isopropylaminothiocarbonylmethylamino, allylaminothiocarbonylamino,but-2-enylaminothiocarbonylamino, pent-2-enylaminothiocarbonylamino,pent-3-enylaminothiocarbonylamino, crotylaminothiocarbonylamino,but-2-ynylaminothiocarbonylamino, pent-2-ynylaminothiocarbonylamino,pent-3-ynylaminothiocarbonylamino,tetrahydrofuran-2-yl-aminothiocarbonylamino,tetrahydropyran-2-yl-aminothiocarbonylamino,adamant-1-yl-aminothiocarbonylamino, cyclopropylaminothiocarbonylamino,N-cyclopropylaminothiocarbonylmethylamino,cyclobutylaminothiocarbonylamino,N-cyclobutylaminothiocarbonyl-methylamino,cyclopentylaminothiocarbonylamino,N-cyclopentylaminothiocarbonylmethylamino,cyclohexylaminothiocarbonylamino,N-cyclohexylaminothiocarbonyl-methylamino,cycloheptylaminothiocarbonylamino,N-cycloheptylaminothiocarbonylmethylamino,cyclopentylmethylaminothiocarbonylamino,N-cyclopentylmethylaminothiocarbonyl-methylamino,cyclohexylmethylaminothiocarbonylamino,N-cyclohexylmethylaminothiocarbonyl-methylamino,dimethylaminothiocarbonylamino, diethylaminothiocarbonylamino,N-((n-hexyl)-aminothiocarbonyl)amino,N-(methyl-(n-hexyl)-aminothiocarbonyl)amino,N-(dimethylamino-thiocarbonyl)-methylamino,N-(dimethylaminothio-carbonyl)-n-pentylamino,N-(diethylaminothiocarbonyl)-methylamino,N-(diethylaminothiocarbonyl)-ethylamino,N-(di-(n-hexyl)-aminothiocarbonyl)-methylamino,N-(di-(n-butyl)-aminothiocarbonyl)-n-butylamino,N-(methyl-(n-hexyl)-aminothiocarbonyl)-methylamino,N(ethyl-(n-pentyl)-aminothiocarbonyl)-ethylamino,N-(methylcyclopentylaminothiocarbonyl)-methylamino,N-(methylcyclohexylaminothiocarbonyl)-ethylamino,benzylaminothiocarbonylamino, phenylaminothiocarbonylamino,fluorophenylaminothiocarbonylamino, chlorophenylaminothiocarbonylamino,bromophenylaminothiocarbonylamino, methylphenylaminothiocarbonylamino,ethylphenylaminothiocarbonylamino,isopropylphenylaminothiocarbonylamino,methoxyphenylaminothiocarbonylamino, ethoxyphenylaminothiocarbonylamino,isopropoxyphenylaminothiocarbonylamino,n-butoxyphenylaminothiocarbonylamino, pyrrolidinocarbonylamino,piperidinocarbonylamino, hexamethyleneiminocarbonylamino,N-pyrrolidinocarbonyl-methylamino, N-pyrrolidinocarbonyl-ethylamino,N-pyrrolidinocarbonyl-isopropylamino,N-pyrrolidinocarbonyl-n-butylamino, N-pyrrolidinocarbonyl-n-pentylamino,N-pyrrolidinocarbonyl-n-hexylamino, N-pyrrolidinocarbonyl-n-octylamino,N-pyrrolidinocarbonyl-n-dodecylamino,N-pyrrolidinocarbonyl-cyclopropylamino,N-pyrrolidinocarbonyl-cyclobutylamino,N-pyrrolidinocarbonyl-cyclopentylamino,N-pyrrolidinocarbonyl-cyclohexylamino,N-pyrrolidinocarbonyl-cycloheptylamino,N-pyrrolidinocarbonyl-cyclopropylmethylamino,N-pyrrolidinocarbonyl-cyclobutylmethylamino,N-pyrrolidinocarbonyl-cyclopentylmethylamino,N-pyrrolidinocarbonyl-cyclohexylmethylamino,N-pyrrolidinocarbonyl-cycloheptylmethylamino,N-pyrrolidinocarbonyl-(2-cyclopropylethyl)-amino,N-pyrrolidinocarbonyl-(2-cyclobutylethyl)-amino,N-pyrrolidinocarbonyl-(2-cyclopentylethyl)-amino,N-pyrrolidinocarbonyl-(2-cyclohexylethyl)-amino,N-pyrrolidinocarbonyl-(2-cycloheptylethyl)-amino,N-pyrrolidinocarbonyl-(3-cyclopropylpropyl)-amino,N-pyrrolidinocarbonyl-(3-cyclobutylpropyl)-amino,N-pyrrolidinocarbonyl-(3-cyclopentylpropyl)-amino,N-pyrrolidinocarbonyl-(3-cyclohexylpropyl)-amino,N-pyrrolidinocarbonyl-(3-cycloheptylpropyl)-amino,N-pyrrolidinocarbonyl-phenylamino, N-pyrrolidinocarbonyl-benzylamino,N-piperidinocarbonyl-methylamino, N-piperidinocarbonyl-ethylamino,N-piperidinocarbonyl-isopropylamino, N-piperidinocarbonyl-n-butylamino,N-piperidinocarbonyl-n-pentylamino, N-piperidinocarbonyl-n-hexylamino,N-piperidinocarbonyl-n-octylamino, N-piperidinocarbonyl-n-dodecylamino,N-piperidinocarbonyl-cyclopropylamino,N-piperidinocarbonyl-cyclobutylamino,N-piperidinocarbonyl-cyclopentylamino,N-piperidinocarbonyl-cyclohexylamino,N-piperidinocarbonyl-cycloheptylamino,N-piperidinocarbonyl-cyclopropylmethylamino,N-piperidinocarbonyl-cyclobutylmethylamino,N-piperidinocarbonyl-cyclopentylmethylamino,N-piperidinocarbonyl-cyclohexylmethylamino,N-piperidinocarbonyl-cycloheptylmethylamino,N-piperidinocarbonyl-(2-cyclopropylethyl)-amino,N-piperidinocarbonyl-(2-cyclobutylethyl)-amino,N-piperidinocarbonyl-(2-cyclopentylethyl)-amino,N-piperidinocarbonyl-(2-cyclohexylethyl)-amino,N-piperidinocarbonyl-(2-cycloheptylethyl)-amino,N-piperidinocarbonyl-(3-cyclopropylpropyl)-amino,N-piperidinocarbonyl-(3-cyclobutylpropyl)-amino,N-piperidinocarbonyl-(3-cyclopentylpropyl)-amino,N-piperidinocarbonyl-(3-cyclohexylpropyl)-amino,N-piperidinocarbonyl-(3-cycloheptylpropyl)-amino,N-piperidinocarbonyl-phenylamino, N-piperidinocarbonyl-benzylamino,N-hexamethyleneiminocarbonyl-methylamino,N-hexamethyleneiminocarbonyl-ethylamino,N-hexamethyleneiminocarbonyl-isopropylamino,N-hexamethyleneiminocarbonyl-n-butylamino,N-hexamethyleneiminocarbonyl-n-pentylamino,N-hexamethyleneiminocarbonyl-n-hexylamino,N-hexamethyleneiminocarbonyl-n-octylamino,N-hexamethyleneiminocarbonyl-n-dodecylamino,N-hexamethyleneiminocarbonyl-cyclopropylamino,N-hexamethyleneiminocarbonyl-cyclobutylamino,N-hexamethyleneiminocarbonyl-cyclopentylamino,N-hexamethyleneiminocarbonyl-cyclohexylamino,N-hexamethyleneiminocarbonyl-cycloheptylamino,N-hexamethyleneiminocarbonyl-cyclopropylmethylamino,N-hexamethyleneiminocarbonyl-cyclobutylmethylamino,N-hexamethyleneiminocarbonyl-cyclopentylmethylamino,N-hexamethyleneiminocarbonyl-cyclohexylmethylamino,N-hexamethyleneiminocarbonyl-cycloheptylmethylamino,N-hexamethyleneiminocarbonyl-(2-cyclopropylethyl)-aminoN-hexamethyleneiminocarbonyl-(2-cyclobutylethyl)-amino,N-hexamethyleneiminocarbonyl-(2-cyclopentylethyl)-aminoN-hexamethyleneiminocarbonyl-(2-cyclohexylethyl)-aminoN-hexamethyleneiminocarbonyl-(2-cycloheptylethyl)-aminoN-hexamethyleneiminocarbonyl-(3-cyclopropylpropyl)-aminoN-hexamethyleneiminocarbonyl-(3-cyclobutylpropyl)-aminoN-hexamethyleneiminocarbonyl-(3-cyclopentylpropyl)-aminoN-hexamethyleneiminocarbonyl-(3-cyclohexylpropyl)-aminoN-hexamethyleneiminocarbonyl-(3-cycloheptylpropyl)-aminoN-hexamethyleneiminocarbonyl-phenylamino,N-hexamethyleneiminocarbonyl-benzylamino,N-morpholinocarbonyl-methylamino, N-morpholinocarbonyl-ethylamino,N-morpholinocarbonyl-isopropylamino, N-morpholinocarbonyl-n-butylamino,N-morpholinocarbonyl-n-pentylamino, N-morpholinocarbonyl-n-hexylamino,N-morpholinocarbonyl-n-octylamino, N-morpholinocarbonyl-n-dodecylamino,N-morpholinocarbonyl-cyclopropylamino,N-morpholinocarbonyl-cyclobutylamino,N-morpholinocarbonyl-cyclopentylamino,N-morpholinocarbonyl-cyclohexylamino,N-morpholinocarbonyl-cycloheptylamino,N-morpholinocarbonyl-cyclopropylmethylamino,N-morpholinocarbonyl-cyclobutylmethylamino,N-morpholinocarbonyl-cyclopentylmethylamino,N-morpholinocarbonyl-cyclohexylmethylamino,N-morpholinocarbonyl-cycloheptylmethylamino,N-morpholinocarbonyl-(2-cyclopropylethyl)-amino,N-morpholinocarbonyl-(2-cyclobutylethyl)-amino,N-morpholinocarbonyl-(2-cyclopentylethyl)-amino,N-morpholinocarbonyl-(2-cyclohexylethyl)-amino,N-morpholinocarbonyl-(2-cycloheptylethyl)-amino,N-morpholinocarbonyl-(3-cyclopropylpropyl)-amino,N-morpholinocarbonyl-(3-cyclobutylpropyl)-amino,N-morpholinocarbonyl-(3-cyclopentylpropyl)-amino,N-morpholinocarbonyl-(3-cyclohexylpropyl)-amino,N-morpholinocarbonyl-(3-cycloheptylpropyl)-amino,N-morpholinocarbonyl-phenylamino, N-morpholinocarbonyl-benzylamino,phthalimino, 5-methoxy-phthalimino, 5,6-dimethoxy-phthalimino,6-methoxy-phthalimino, homophthalimino, 4,4-dimethyl-homophthalimino,7-methoxy-homophthalimino, 6,7-dimethoxy-homophthalimino,7-methoxy-4,4-diethyl-homophthalimino,6,7-dimethoxy-4,4-dimethyl-homophthalimino,1,2,3,6-tetrahydrophthalimino, hexahydrophthalimino,1-oxo-isoindolin-2-yl, 3,4-dimethyl-phthalimino,4,5-dimethyl-1,2,3,6-tetrahydrophthalimino,4,5-dimethyl-hexahydrophthalimino, 4,5-dimethyl-1-oxo-isoindolin-2-yl,3,4-dimethoxy-phthalimino, 4,5-dimethoxy-1,2,3,6-tetrahydrophthalimino,4,5-dimethoxy-hexahydrophthalimino, 4,5dimethoxy-1-oxo-isoindolin-2-yl,glutarimino, 3,3-tetramethylene-glutarimino,3,3-pentamethylene-glutarimino, 2,2-dimethyl-glutarimino,3-methyl-glutarimino, 3,3dimethyl-glutarimino, 3-ethyl-glutarimino,hexafluoro-glutarimino, 3-ethyl-3-methyl-glutarimino,1,3-cyclopentanedicarbonylimino, 2,4-dimethyl-glutarimino,1,3-cyclopentanedicarbonylimino, 2,4-dimethyl-glutarimino,2,4-di-n-propyl-glutarimino, endo-bicyclo2,2,2!oct-5-ene-2,3-dicarboxylic acid-imino,methyl-5-norbornene-2,3-di-carboxylic acid-imino,3,6-endoxo-1,2,3,6-tetrahydrophthalimino or5-norbornene-endo-2,3-dicarboxylic acid-imino group,

for R₂ the meanings mentioned above for R₁ or 1H-tetrazol-5-yl,2-imidazolidon-1-yl, 3-methyl-2-imidazolidon-1-yl,3-ethyl-2-imidazolidon-1-yl, 3-n-propyl-2-imidazolidon-1-yl,3-isopropyl-2-imidazolidon-1-yl, 3-cyclopropyl-2-imidazolidon-1-yl,3-cyclobutyl-2-imidazolidon-1-yl, 3-cyclopentyl-2-imidazolidon-1-yl,3-cyclohexyl-2-imidazolidon-1-yl, 3-cycloheptyl-2imidazolidon-1-yl,3-cyclopropylmethyl-2-imidazolidon-1-yl,3-cyclobutylmethyl-2-imidazolidon-1-yl,3-cyclopentylmethyl-2-imidazolidon-1-yl,3-cyclohexylmethyl-2imidazolidon-1-yl,3-cycloheptylmethyl-2-imidazolidon-1-yl,3-(2-cyclopropylethyl)-2-imidazolidon-1-yl,3-(2-cyclobutylethyl)-2-imidazolidon-1-yl,3-(2-cyclopentylethyl)-2-imidazolidon-1-yl,3-(2-cyclohexylethyl)-2-imidazolidon-1-yl,3-(2-cycloheptylethyl)-2-imidazolidon-1-yl,3-(3-cyclopropylpropyl)-2-imidazolidon-1-yl,3-(3-cyclobutylpropyl)-2-imidazolidon-1-yl,3-(3-cyclopentylpropyl)-2-imidazolidon-1-yl,3-(3-cyclohexylpropyl)-2-imidazolidon-1-yl,3-(3-cycloheptylpropyl)-2-imidazolidon-1-yl,3-benzyl-2-imidazolidon-1-yl, 3-(2-phenylethyl)-2-imidazolidon-1-yl,3-(3-phenylpropyl)-2-imidazolidon-1-yl,3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-methyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-ethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-n-propyl-3,4,5,6-tetrahydro-2pyrimidon-1-yl,3-isopropyl-3,4,5,6-tetrahydro-2pyrimidon-1-yl,3-cyclopropyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclobutyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclopentyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclohexyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cycloheptyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclopropylmethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclobutylmethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclopentylmethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cyclohexylmethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-cycloheptylmethyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(2-cyclopropylethyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(2-cyclobutylethyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(2-cyclopentylethyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(2-cyclohexylethyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(2-cycloheptylethyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(3-cyclopropyl-propyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(3-cyclobutylpropyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(3-cyclopentylpropyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(3-cyclohexylpropyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(3-cycloheptylpropyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-benzyl-3,4,5,6-tetrahydro-2-pyrimidon-1-yl,3-(2-phenylethyl)-3,4,5,6-tetrahydro-2-pyrimidon-1-yl or3-(3-phenylpropyl)-3,4,5,6-tetra-hydro-2-pyrimidon-1-yl group,

for R₃ those of hydrogen, fluorine, chlorine or bromine atom, methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert.butyl, n-pentyl,n-hexyl, 1-methylpropyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl,1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl,1-ethylpropyl, 1,1-diethylethyl, methoxymethyl, ethoxymethol,(2-hydroxyethoxy)-methyl, 2-methoxyethyl, 2-ethoxyethyl,3-methoxypropyl, methylmercaptomethyl, 2-methylmercapto-ethyl,3-methylmercapto-propyl, 4methylmercapto-butyl, methylsulphinyl-methyl,2-methylsulphinyl-ethyl, 3-methylsulphinyl-propyl,4-methylsulphinyl-butyl, methylsulphonyl-methyl,2-methylsulphonyl-ethyl, 3-methylsulphonyl-propyl,4-methylsulphonyl-butyl, 2-methylamino-ethyl, 3-methylamino-propyl,4-methylamino-butyl, 2-dimethylamino-ethyl, 3-dimethylamino-propyl,4-dimethylamino-butyl, 5-dimethylamino-pentyl, 2-diethylamino-ethyl,2-di-n-propylamino-ethyl, 2-(2-hydroxyethoxy)-ethyl,3-(2-hydroxyethoxy)-propyl, 2-(2-methoxyethoxy)-ethyl,2-(2-methoxyethoxy)-isopropyl, 3-(2-methoxyethoxy)-propyl,2-(2-ethoxyethoxy)-ethyl, 2-(2-ethoxyethoxy)-isopropyl,3-(2-ethoxyethoxy)-propyl, 2-(2-isopropoxyethoxy)-ethyl, methoxy,ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-hydroxyethoxy,3-hydroxypropoxy, 2-methoxyethoxy, 2-ethoxyethoxy, 2-isopropoxyethoxy,3-methoxypropoxy, 3-isopropoxypropoxy, mercapto, methylmercapto,ethylmercapto, n-propylmercapto, isopropylmercapto, n-butylmercapto,benzyl, 2-phenylethyl, 3-phenylpropyl, allyl, n-but-2-enyl,n-pent-2-enyl, n-prop-1-enyl, n-but-1-enyl, n-pent-1-enyl, n-but-3-enyl,n-pent-3-enyl, n-pent-4-enyl, propargyl, n-but-3-ynyl, n-pent-3-ynyl,n-pent-4ynyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentylmethyl,cyclohexylmethyl, cycloheptylmethyl, 2-cyclopentylethyl,2-cyclohexyl-ethyl, 2-cycloheptylethyl, 3-cyclopentylpropyl,3-cyclohexylpropyl, phenyl, hydroxyphenyl, fluorophenyl, chlorophenyl,bromophenyl, methylphenyl, ethylphenyl, isopropylphenyl, methoxyphenyl,ethoxyphenyl, n-propoxyphenyl, n-butoxyphenyl, hydroxy,(imidazol-4-yl)methylamino, 2-(imidazol-4-yl)ethylamino,3-(imidazol-4-yl)propylamino, methylamino, ethylamino, n-propylamino,isopropylamino, n-butylamino, isobutylamino, aminocarbonyl,methylaminocarbonyl, ethylaminocarbonyl, isopropylaminocarbonyl,n-butylaminocarbonyl, cyclopentylaminocarbonyl, cyclohexylaminocarbonyl,cycloheptylaminocarbonyl, naphthyl, pyridyl, pyrimidyl, pyridazinyl,pyrazinyl, pyrazolyl, 1,3-dimethylpyrazolyl, pyrrolyl, imidazolyl,oxazolyl, thiazolyl, triazolyl or tetrazolyl group, and

for R₄ those of carboxy, methoxycarbonyl, ethoxycarbonyl,n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,isobutoxycarbonyl, tert.butoxycarbonyl, n-pentoxycarbonyl,n-hexoxycarbonyl, benzyloxycarbonyl, 1-phenylethoxycarbonyl,2-phenyl-ethoxycarbonyl, 3-phenylpropoxycarbonyl,pivaloyloxymethoxycarbonyl, phthalidyloxycarbonyl,ethoxycarbonyloxyethoxycarbonyl, methoxymethoxycarbonyl,cyclohexyloxycarbonylmethoxycarbonyl,(1,3-dioxa-2-oxo-4-methyl-cyclopentan-5-yl)-methoxycarbonyl, amino,phthalimido, aminoacetylamino, methoxycarbonylaminoacetylamino,ethoxycarbonylaminoacetylamino, isopropoxycarbonylaminoacetylamino,n-butoxycarbonylaminoacetylamino, methylcarbonylamino,trifluoromethylcarbonylamino, ethylcarbonylamino, n-propylcarbonylamino,isopropylcarbonylamino, cyclopentylcarbonylamino,cyclohexylcarbonylamino, cycloheptylcarbonylamino, phenylcarbonylamino,fluorophenylcarbonylamino, chlorophenylcarbonylamino,bromophenylcarbonylamino, methylphenylcarbonylamino,ethylphenylcarbonylamino, isopropylphenylcarbonylamino,methoxyphenylcarbonylamino, ethoxyphenylcarbonylamino,n-propoxyphenylcarbonylamino, benzylcarbonylamino,2-phenylethylcarbonylamino, methylsulphonylamino,trifluoromethylsulphonylamino, ethylsulphonylamino,n-propylsulphonylamino, isopropylsulphonylamino, phenylsulphonylamino,fluorophenylsulphonylamino, chlorophenylsulphonylamino,bromophenylsulphonylamino, methylphenylsulphonylamino,ethylphenylsulphonylamino, isopropylphenylsulphonylamino,methoxyphenylsulphonylamino, ethoxyphenylsulphonylamino,benzylsulphonylamino, cyano, aminomethyl, methylsulphonylaminomethyl,ethylsulphonylaminomethyl, n-propylsulphonylaminomethyl,phenylsulphonylaminomethyl, methylphenylsulphonylaminomethyl,trifluoromethylsulphonylaminomethyl, methylsulphonylaminocarbonyl,ethylsulphonylaminocarbonyl, n-propylsulphonylaminocarbonyl,isopropylsulphonylaminocarbonyl, n-butylsulphonylaminocarbonyl,trifluoromethylsulphonylaminocarbonyl,perfluoro-n-butylsulphonylaminocarbonyl, phenylsulphonylaminocarbonyl,benzylsulphonylaminocarbonyl, 4-methylphenylsulphonylaminocarbonyl,4-chlorophenylsulphonylaminocarbonyl, trifluoroacetylaminomethyl,1H-tetrazolyl or 1-(triphenylmethyl)-tetrazolyl group.

Preferred compounds of the general formula I are those in which

R₁ denotes a hydrogen, fluorine or chlorine atom, a trifluoromethyl,hydroxy, benzyloxy, carboxy, cyano, amino, nitro, aminosulphonyl,methylaminosulphonyl, dimethylaminosulphonyl,trifluoromethylsulphonyloxy or tetrazolyl group,

an alkyl group having 1 to 4 carbon atoms, wherein the methyl group maybe additionally substituted by a hydroxy or alkylamino group having 1 to4 carbon atoms,

an alkoxy group having 1 to 4 carbon atoms, which may be substituted inthe 2, 3 or 4 position by a hydroxy, alkoxy, alkylamino, dialkylamino orimidazolyl group and the alkyl substituent may contain 1 to 3 carbonatoms in each case,

an alkanoyloxy group having 1 to 4 carbon atoms or acycloalkylaminocarbonyloxy group having 5 to 7 carbon atoms in thecycloalkyl moiety,

an amino group, which is substituted by a benzyl, Decalin,trifluoromethylcarbonyl, benzylcarbonyl, benzyloxycarbonyl,2-ethyl-5-methylcyclohexyloxy or tert.butoxycarbonylaminoacetyl group,by an alkyl group having 1 to 5 carbon atoms, by a cycloalkyl,cycloalkylalkyl, cycloalkoxycarbonyl, cycloalkylcarbonyl orcycloalkylalkanoyl group, wherein the cycloalkyl moiety may contain 5 to7 carbon atoms, the alkyl moiety may contain 1 to 3 carbon atoms and thealkanoyl moiety may contain 1 to 3 carbon atoms, by an alkanoyl grouphaving 1 to 6 carbon atoms, by an aminoalkanoyl or dialkylaminoalkanoylgroup, in which the alkyl moiety and the alkanoyl moiety may eachcontain 1 to 3 carbon atoms by an alkoxycarbonyl group having a total of2 to 7 carbon atoms, by an alkylsulphonyl group having 1 to 4 carbonatoms or by a thiazolidin-3-ylcarbonyl group substituted by analkoxycarbonyl group having a total of 2 to 4 carbon atoms,

a benzylamino or alkylamino group having 1 to 5 carbon atoms, which issubstituted at the nitrogen atom additionally by a benzyl or cyclohexylgroup, by an alkyl group having 1 to 3 carbon atoms, which may besubstituted in the 2 or 3 position by an alkoxy group having 1 to 3carbon atoms or by a phenylamino group, by an alkanoyl group having 1 to5 carbon atoms, which may be substituted by an alkoxy group having 1 to3 carbon atoms, by a cycloalkylcarbonyl group having a total of 6 to 8carbon atoms or by an alkoxycarbonyl group having a total of 2 to 4carbon atoms,

a carbonyl group, which is substituted by an alkyl group which may besubstituted in the 2- or 3-position by a hydroxy, alkoxycarbonyl oralkylamino group, by an alkylamino group with 1 to 5 carbon atoms whichmay be substituted by a carboxy group in the alkyl moiety, by analkylamino group substituted by a phenylamino group in the 2- or3-position, by a phenyl, alkoxy, amino, benzylamino, phenylethylamino,cycloalkylamino or cycloalkylalkylamino, in which the alkyl moiety maycontain 1 to 3 carbon atoms and the cycloalkyl moiety may contain 5 to 7carbon atoms, and additionally a C₁₋₅ alkylamino group may besubstituted at the nitrogen atom by an alkyl group having 1 to 4 carbonatoms,

an aminocarbonylamino or aminothiocarbonylamino group, which may bemonosubstituted, disubstituted or trisubstituted by an alkyl grouphaving 1 to 12 carbon atoms, by an alkenyl or alkynyl group having 3 tocarbon atoms in each case, by a bicyclic or tricyclic alkyl group having7 to 11 carbon atoms, by a cycloalkyl, cycloalkylalkyl or phenylalkylgroup, wherein the substituents may be the same or different, and thealkyl moiety may contain 1 to 3 carbon atoms and the cycloalkyl moietymay contain 5 to 7 carbon atoms, and a methylene group in a cycloalkylradical having 5 to 7 carbon atoms may be replaced by an oxygen atom,and an alkyl group may be substituted in the 4, 5 or 6 position by ahydroxy or trifluoroacetyl group,

a cycloalkyleneiminocarbonylamino group having 4 to 6 carbon atoms inthe cycloalkyleneimino moiety or a morpholinocarbonylamino group, whichmay both be substituted at the amino nitrogen by an alkyl group having 1to 12 carbon atoms, by a cycloalkyl, cycloalkylalkyl or phenylalkylgroup, in which the alkyl moiety may contain 1 to 3 carbon atoms and thecycloalkyl moiety may contain 5 to 7 carbon atoms,

a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino,2-carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, whilst a carbonyl group ina phthalimino group may be replaced by a methylene group and a methylenegroup in a homophthalimino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted by one ortwo alkyl groups, and additionally the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, whilst thesubstituents may be identical or different, and at the same time theymay be partially or wholly hydrogenated, a bicycloalkane-3-carboxylicacid amino or bicycloalkene-3-carboxylic acid amino group substituted bya carboxy group in the 2-position, a bicycloalkane-2,3-dicarboxylic acidimino or bicycloalkene-2,3-dicarboxylic acid imino group, wherein thebicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms,may be substituted by 1, 2 or 3 methyl groups and an endomethylene groupmay be replaced by an oxygen atom, a glutaric acid imino or3-carboxy-n-propylene-carbonyl group wherein the n-propylene group maybe perfluorinated, substituted by one or two alkyl groups or by atetramethylene or pentamethylene group, or

a 5,7-dioxa-1H,3H-imidazo 1,5-c!thiazolyl group, a 2-imidazolidon-1-ylgroup optionally substituted in the 3 position by an alkyl group having1 to 3 carbon atoms, or a 3,4,5,6-tetrahydro-2-pyrimidon-1-yl group,

R₂ denotes a hydrogen, fluorine or chlorine, a methyl, hydroxy ormethoxy group, or

R₁ and R₂ together with the two ortho position carbon atoms of theneighbouring phenyl ring denote a phenyl or1-alkyl-3,3-dialkyl-2,3-dihydro-pyrrol-2-one group, in which the alkylmoiety may contain 1 to 3 carbon atoms in each case,

R₃ denotes a hydrogen, fluorine or chlorine atom,

a hydroxy, benzyl or aminocarbonyl group,

an alkyl group having 1 to 5 carbon atoms, wherein the methyl group maybe additionally substituted by a hydroxy group, by an alkoxy,alkylsulphenyl, alkylsulphinyl or alkylsulphonyl group each having 1 to3 carbon atoms, a cycloalkyl or cycloalkylalkyl group, in which thecycloalkyl moiety may contain 5 to 7 carbon atoms and the alkyl moietymay contain 1 to 3 carbon atoms, an alkenyl or alkynyl group each having3 to 5 carbon atoms, a phenylalkyl group having 1 to 3 carbon atoms,

an alkylamino group having 1 to 4 carbon atoms,

a pyridyl, furyl, thiazolyl or pyrazolyl group, which may be substitutedby one or two methyl groups,

R₄ denotes an alkoxycarbonyl having a total of 1 to 5 carbon atoms, anamino, phthalimino, aminomethyl, carboxy, cyano,methylsulphonylaminocarbonyl, trifluoromethylsulphonylaminocarbonyl,benzenesulphonylaminocarbonyl, trifluorocarbonylaminomethyl,trifluoromethylaminomethyl, tetrazolyl or 1-(triphenylmethyl)tetrazolylgroup,

R₅ denotes a hydrogen, fluorine, chlorine or bromine atom,

R₆ denotes a hydrogen atom or

R₅ and R₄ together with the two ortho position carbon atoms denote aphenyl group, and 1 and 3 isomer mixtures thereof and the addition saltsthereof, in particular for pharmaceutical application theirphysiologically acceptable addition salts with inorganic or organicacids.

However, particularly preferred compounds of the general formula I arethose in which

R₁ denotes an amino group, which is substituted by a benzyl, Decalin,trifluoromethylcarbonyl, benzylcarbonyl, benzyloxycarbonyl,2-ethyl-5-methylcyclohexyloxy or tert-butoxycarbonylaminoacetyl group,by an alkyl group having 1 to 5 carbon atoms, by acycloalkyl,cycloalkylalkyl, cycloalkoxycarbonyl, cycloalkylcarbonyl orcycloalkylalkanoyl group, wherein the cycloalkyl moiety may contain 5 to7 carbon atoms, the alkyl moiety may contain 1 to 3 carbon atoms and thealkanoyl moiety may contain 1 to 3 carbon atoms, by an alkanoyl grouphaving 1 to 6 carbon atoms, by an aminoalkanoyl or dialkylaminoalkanoylgroup, in which the alkyl moiety and the alkanoyl moiety may eachcontain 1 to 3 carbon atoms, by an alkoxycarbonyl group having a totalof 2 to 7 carbon atoms, by an alkylsulphonyl group having 1 to 4 carbonatoms or by a thiazolidin-3-ylcarbonyl group substituted by analkoxycarbonyl group having a total of 2 to 4 carbon atoms,

a benzylamino or alkylamino group having 1 to 5 carbon atoms, which isadditionally substituted at the nitrogen atom by a benzyl or cyclohexylgroup, by an alkyl group having 1 to 3 carbon atoms, which may besubstituted in the 2 or 3 position by an alkoxy group having 1 to 3carbon atoms or by a phenylamino group, by an alkanoyl group having 1 to5 carbon atoms, which may be substituted by an alkoxy group having 1 to3 carbon atoms, by a cycloalkylcarbonyl group having a total of 6 to 8carbon atoms or by an alkoxycarbonyl group having a total of 2 to 4carbon atoms,

an aminocarbonylamino or aminothiocarbonylamino group, which may bemonosubstituted, disubstituted or trisubstituted by an alkyl grouphaving 1 to 12 carbon atoms, by an alkenyl or alkynyl group each having3 to 5 carbon atoms, by a bicyclic or tricyclic alkyl group having 7 to11 carbon atoms, by a cycloalkyl, cycloalkylalkyl or phenylalkyl group,wherein the substituents may be the same or different, and the alkylmoiety may contain 1 to 3 carbon atoms and the cycloalkyl moiety maycontain 5 to 7 carbon atoms, and a methylene group in a cycloalkylradical having 5 to 7 carbon atoms may be replaced by an oxygen atom,and an alkyl group may be substituted in the 4, 5 or 6 position by ahydroxy or trifluoroacetyl group,

a cycloalkyleneiminocarbonylamino group having 4 to 6 carbon atoms inthe cycloalkyleneimino moiety or a morpholinocarbonylamino group, whichmay both be substituted at the amino nitrogen by an alkyl group having 1to 12 carbon atoms, by a cycloalkyl, cycloalkylalkyl or phenylalkylgroup, in which the alkyl moiety may contain 1 to 3 carbon atoms and thecycloalkyl moiety may contain 5 to 7 carbon atoms,

a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino,2-carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, whilst a carbonyl group ina phthalimino group may be replaced by a methylene group and a methylenegroup in a homophthalimino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted by one ortwo alkyl groups, and additionally the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, whilst thesubstituents may be identical or different, and at the same time theymay be partially or wholly hydrogenated, a bicycloalkane-3-carboxylicacid amino or bicycloalkene-3-carboxylic acid amino group substituted bya carboxy group in the 2-position, a bicycloalkane-2,3-dicarboxylic acidimino or bicycloalkene-2,3dicarboxylic acid imino group, wherein thebicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms,may be substituted by 1, 2 or 3 methyl groups and an endomethylene groupmay be replaced by an oxygen atom, a glutaric acid imino or3-carboxy-n-propylene-carbonyl group wherein the n-propylene group maybe perfluorinated, substituted by one or two alkyl groups or by atetramethylene or pentamethylene group, or

a 5,7-dioxa-1H,3H-imidazo 1,5-c!thiazolyl group,

R₂ denotes a hydrogen atom, a methyl or hydroxy group, or

R₁ and R₂ together with the two ortho position carbon atoms of theneighbouring phenyl ring denote a phenyl group,

R₃ denotes an alkyl group having 3 to 5 carbon atoms, an alkenyl oralkynyl group each having 3 to 5 carbon atoms,

R₄ denotes a carboxy, methylsulphonylaminocarbonyl,trifluoromethylsulphonylaminocarbonyl, benzenesulphonylaminocarbonyl,trifluorocarbonylaminomethyl, trifluoromethylaminomethyl or tetrazolylgroup,

R₅ denotes a hydrogen atom,

R₆ denotes a hydrogen atom or

R₅ and R₆ together with the two ortho position carbon atoms denote aphenyl group,

in particular those compounds of the general formula I in which

R₁ denotes an amino group, which is substituted by an alkanoyl grouphaving 1 to 6 carbon atoms, by an aminoalkanoyl or dialkylaminoalkanoylgroup, in which the alkyl moiety and the alkanoyl moiety may eachcontain 1 to 3 carbon atoms, by an alkoxycarbonyl group having a totalof 2 to 7 carbon atoms or by a thiazolidin-3-ylcarbonyl groupsubstituted by an alkoxycarbonyl group having a total of 2 to 4 carbonatoms,

a benzylamino or alkylamino group having 1 to 5 carbon atoms, which issubstituted at the nitrogen atom by an alkanoyl group having 1 to 5carbon atoms, which may be substituted by an alkoxy group having 1 to 3carbon atoms, by a cycloalkylcarbonyl group having a total of 6 to 8carbon atoms or by an alkoxycarbonyl group having a total of 2 to 4carbon atoms,

an aminocarbonylamino or aminothiocarbonylamino group, which may bemonosubstituted, disubstituted or trisubstituted by an alkyl grouphaving 1 to 8 carbon atoms, by an alkenyl or alkynyl group each having 3to 5 carbon atoms, by a bicyclic or tricyclic alkyl group having 7 to 11carbon atoms, by a cycloalkyl, cycloalkylalkyl or phenylalkyl group,wherein the substituents may be the same or different, and the alkylmoiety may contain 1 to 3 carbon atoms and the cycloalkyl moiety maycontain 5 to 7 carbon atoms, and a methylene group in a cycloalkylradical having 5 to 7 carbon atoms may be replaced by an oxygen atom,and an alkyl group may be substituted in the 4, 5 or 6 position by ahydroxy or trifluoroacetyl group,

a cycloalkyleneiminocarbonylamino group having 4 to 6 carbon atoms inthe cycloalkyleneimino moiety or a morpholinocarbonylamino group, whichmay both be substituted at the amino nitrogen by an alkyl group having 1to 8 carbon atoms, by a cycloalkyl, cycloalkylalkyl or phenylalkylgroup, in which the alkyl moiety may contain 1 to 3 carbon atoms and thecycloalkyl moiety may contain 5 to 7 carbon atoms,

a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino,2-carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, whilst a carbonyl group ina phthalimino group may be replaced by a methylene group and a methylenegroup in a homophthalimino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted by one ortwo alkyl groups, and additionally the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, whilst thesubstituents may be identical or different, and at the same time theymay be partially or wholly hydrogenated, a bicycloalkane-3-carboxylicacid amino or bicycloalkene-3-carboxylic acid amino group substituted bya carboxy group in the 2-position, a bicycloalkane-2,3-dicarboxylic acidimino or bicycloalkene-2,3-dicarboxylic acid imino group, wherein thebicycloalkane and bicycloalkane parts each contain 9 or 10 carbon atoms,may be substituted by 1, 2 or 3 methyl groups and an endomethylene groupmay be replaced by an oxygen atom, a glutaric acid imino or3-carboxy-n-propylene-carbonyl group wherein the n-propylene group maybe perfluorinated, substituted by one or two alkyl groups or by atetramethylene or pentamethylene group, or a 5,7-dioxa-1H,3H-imidazo1,5-c!thiazolyl group,

R₂ denotes a hydrogen atom, or

R₁ and R₂ together with the two ortho position carbon atoms of theneighbouring phenyl ring denote a phenyl group,

R₃ denotes an alkyl group having 3 to 5 carbon atoms, an alkenyl oralkynyl group each having 3 to 5 carbon atoms,

R₄ denotes a carboxy or tetrazolyl group,

R₅ denotes a hydrogen atom,

R₆ denotes a hydrogen atom or

R₅ and R₆ together with the two ortho position carbon atoms denote aphenyl group,

1-isomer and 3-isomer mixtures thereof and addition salts thereof, inparticular for pharmaceutical application their physiologicallyacceptable addition salts with inorganic or organic acids.

The novel compounds of the formula I are obtained in accordance with theinvention by the following processes:

a) cyclisation of a compound of the formula ##STR3## in which R₁ and R₂are as hereinbefore defined, one of the radicals X₁ or Y₁ is a group ofthe formula ##STR4## and the other of the radicals X₁ or Y₁ is a groupof the formula ##STR5## wherein R₃ ' as hereinbefore defined for R₃,with the exception of the fluorine, chlorine or bromine atom, thehydroxy, mercapto or aminocarbonyl group, wherein the latter may besubstituted by an alkyl group having 1 to 3 carbon atoms or by acycloalkyl group having 5 to 7 carbon atoms,

R₄ to R₆ are as hereinbefore defined,

R₇ denotes a hydrogen atom, a hydroxy group or an R₃ 'CO group, whereinR₃ ' is defined as above,

Z₁ and Z₂, which may be the same or different, denote optionallysubstituted amino groups or hydroxy or mercapto groups optionallysubstituted by lower alkyl groups, or

Z₁ and Z₂, together denote an oxygen or sulphur atom, an imino groupoptionally substituted by an alkyl group having 1 to 3 carbon atoms, analkylenedioxy or alkylenedithio group each having 2 or 3 carbon atoms,but wherein one of the radicals X₁ or Y₁ must be a group of the formula##STR6##

The cyclisation is advantageously carried out in a solvent or solventmixture, such as ethanol, isopropanol, glacial acetic acid, benzene,chlorobenzene, toluene, xylene, glycol, glycolmonomethylether,diethyleneglycoldimethylether, sulpholane, dimethylformamide, Tetralinor in an excess of the acylating agent used for the preparation of thecompound of the general formula II, for example in the correspondingnitrile, anhydride, acid halide, ester or amide, for example attemperatures between 0° and 250° C., but preferably at the boilingtemperature of the reaction mixture, optionally in the presence of acondensation agent, such as phosphorusoxychloride, thionylchloride,sulphurylchloride, sulphuric acid, p-toluenesulphonic acid,methanesulphonic acid, hydrochloric acid, phosphoric acid,polyphosphoric acid, acetic anhydride, or optionally also in thepresence of a base, such as potassium ethoxide or potassiumtert.butoxide. However, cyclisation may also be carried out without asolvent and/or condensing agent.

However, the reaction is particularly advantageously carried out bypreparing a compound of the formula II in the reaction mixture byreducing a corresponding o-nitroamino compound, optionally in thepresence of a carboxylic acid of the formula R₃ 'COOH, or by acylationof a corresponding o-diamino compound. When the reduction of the nitrogroup is terminated at the hydroxylamine step, the N oxide of a compoundof the formula I is obtained in the subsequent cyclisation. The N oxidethus obtained is then converted to a corresponding compound of theformula I by means of reduction.

The subsequent reduction of the N oxide of formula I obtained ispreferably carried out in a solvent, such as water, water/ethanol,methanol, glacial acetic acid, ethyl acetate or dimethylformamide, withhydrogen in the presence of a hydrogenation catalyst, such as Raneynickel, platinum or palladium/carbon, with metals, such as iron, tin orzinc in the presence of an acid such as acetic acid, hydrochloric acidor sulphuric acid, with salts, such as iron (II) sulphate, tin (II)chloride or sodium dithionite, or with hydrazine in the presence ofRaney nickel, at temperatures between 0° and 50° C., but preferably atambient temperature.

A 2-alkoxy compound of formula I optionally thus obtained, can then beconverted to a corresponding 2-hydroxy compound of formula I, optionallyby means of hydrolysis, preferably in the presence of an acid, such ashydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid ortrichloroacetic acid, in a suitable solvent, such as water,water/methanol, ethanol, water/ethanol, water/isopropanol orwater/dioxane, at temperatures between -10° and 120° C., for example attemperatures between 20° C. and the boiling temperature of the reactionmixture.

b) For the preparation of the compounds of formula I, in which R₃represents the aromatic or heteroaromatic radicals mentionedhereinbefore for R₃ :

Reaction of phenylenediamine of the formula ##STR7## (in which R₁ and R₂are as hereinbefore defined, one of the radicals X₂ or Y₂ denotes agroup of the formula ##STR8## in which R₄ to R₆ are as hereinbeforedefined, and the other of the radicals X₂ or Y₂ denotes an amino group)with an aldehyde of the formula

    OCH--R.sub.3 "                                             (IV)

in which

R₃ " denotes an aromatic or heteroaromatic radical as hereinbeforedefined for R₃.

The reaction is preferably carried out in a suitable solvent, such asbenzene, toluene, xylene, mesitylene or dimethylacetamide, in thepresence of a oxidising agent, such as sulphur or air oxygen, attemperatures between 80° and 250° C., preferably at the boilingtemperature of the reaction mixture.

A 2-alkoxy compound of formula I optionally thus obtained can then beconverted to a corresponding 2-hydroxy compound of formula I, optionallyby means of hydrolysis, preferably in the presence of an acid, such ashydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid ortrichloroacetic acid, in a suitable solvent, such as water,water/methanol, ethanol, water/ethanol, water/isopropanol orwater/dioxane, at temperatures between -10° and 120° C., for example attemperatures between 20° C. and the boiling temperature of the reactionmixture.

c) For the preparation of compounds of the formula I, in which at leastone of the radicals R₁, R₂ and/or R₃ is one of the radicals containing asulphinyl or sulphonyl group as hereinbefore defined for R₁, R₂ and/orR₃, and the remainder of the radicals R₁, R₂ and/or R₃ are ashereinbefore defined:

Oxidation of a compound of the formula ##STR9## in which R₄ to R₆ are ashereinbefore defined,

at least one of the radicals R₁ ', R₂ ' and/or R₃ '" is one of theradicals containing a sulphur atom or a sulphinyl group as hereinbeforedefined for R₁, R₂ and/or R₃, and the remainder of the radicals R₁ ', R₂' and/or R₃ '" have the meanings hereinbefore defined for R₁, R₂ and/orR₃.

The oxidation is preferably carried out in a solvent or solvent mixture,for example in water, water/pyridine, acetone, glacial acetic acid,dilute sulphuric acid or trifluoroacetic acid, advantageously attemperatures between -80° and 100° C., depending on the oxidising agentused.

For the preparation of a sulphinyl compound of the formula I, theoxidation is advantageously carried out using one equivalent of theoxidising agent used, for example using hydrogen peroxide in glacialacetic acid, trifluoroacetic acid or formic acid at 0° to 20° C. or inacetone at 0° to 60° C. using a peracid, such as performic acid inglacial acetic acid or trifluoroacetic acid at 0° to 50° C., or usingm-chloroperbenzoic acid in methylene chloride or chloroform at -20° to60° C., using sodium metaperiodate in aqueous methanol or ethanol at-15° to 25° C., using bromine in glacial acetic acid or aqueous aceticacid, using N-bromosuccinimide in ethanol, using tert.butyl hypochloritein methanol at -80° to -30° C., using iodobenzodichloride in aqueouspyridine at 0° to 50° C., using nitric acid in glacial acetic acid at 0°to 20° C., using chromic acid in glacial acetic acid or in acetone at 0°to 20° C., and using sulphuryl chloride in methylene chloride at -70°C., the thioether-chlorine complex thus obtained is advantageouslyhydrolysed using aqueous ethanol.

For the preparation of a sulphonyl compound of the formula I, theoxidation is advantageously carried out using one or using two or moreequivalents of the oxidising agent used, for example using hydrogenperoxide in glacial acetic acid, trifluoroacetic acid or in formic acidat 20° to 100° C., or in acetone at 0° to 60° C., using a peracid, suchas performic acid or m-chloroperbenzoic acid in glacial acetic acid,trifluoroacetic acid, methylene chloride or chloroform at temperaturesbetween 0° and 60° C., using nitric acid in glacial acetic acid at 0° to20° C., using chromic acid or potassium permanganate in glacial aceticacid, water/sulphuric acid or in acetone at 0° to 20° C.

d) For the preparation of a compound of the formula I, in which R₄ is acarboxy or amino group:

Conversion of a compound of the formula ##STR10## in which R₁ to R₂, R₃and R₄ are as hereinbefore defined, and R₄ ' is a group which can beconverted to a carboxy group by means of hydrolysis, thermolysis orhydrogenolysis, or a group which can be converted to an amino group bymeans of hydrolysis, hydrogenolysis or transamidation.

For example, functional derivatives of the carboxy group, such as itsunsubstituted or substituted amides, esters, thiolesters, orthoesters,iminoethers, amidines or anhydrides, the nitrile group or the tetrazolylgroup, can be converted to a carboxy group by means of hydrolysis,esters of tertiary alcohols, for example tert.butylester, can beconverted to a carboxy group by means of thermolysis, esters ofaralkanols, for example benzyl ester, can be converted to a carboxygroup by means of hydrogenolysis, acylamino groups, for example thebenzoylamino or phthalimido group, can be converted to an amino group bymeans of hydrolysis and imino groups, for example the phthalimino group,can be converted to an amino group by means of transamidation.

The hydrolysis is advantageously carried out either in the presence ofan acid, such as hydrochloric acid, sulphuric acid, phosphoric acid,trichloroacetic acid or trifluoroacetic acid, in the presence of a base,such as sodium hydroxide or potassium hydroxide, in a suitable solvent,such as water, water/methanol, ethanol water/ethanol, water/isopropanolor water/dioxane, at temperatures between -10° C. and 120° C., forexample at temperatures between ambient temperature and the boilingtemperature of the reaction mixture. During hydrolysis in the presenceof an organic acid, such as trichloroacetic acid or trifluoroaceticacid, alcohol hydroxy groups, which are optionally present, may also beconverted to a corresponding acyloxy group, such as the trifluoroacetoxygroup.

If R₄ ' in a compound of formula VI denotes a cyano or aminocarbonylgroup, these groups may also be converted to the carboxy group using anitrite, for example sodium nitrite, in the presence of an acid, such assulphuric acid, this advantageously being used at the same time assolvent, at temperatures between 0° and 50° C.

If R₄ ' in a compound of formula VI denotes, for example thetert.butyloxycarbonyl group, the tert.butyl group may also be cleavedthermally, optionally in a inert solvent, such as methylene chloride,chloroform, benzene, toluene, tetrahydrofuran or dioxane, and preferablyin the presence of a catalytic amount of an acid, such asp-toluenesulphonic acid, sulphuric acid, phosphoric acid orpolyphosphoric acid, preferably at the boiling temperature of thesolvent used, for example at temperatures between 40° C. and 100° C.

If R₄ ' in a compound of formula VI denotes, for example thebenzyloxycarbonyl group, the benzyl group may also be cleavedhydrogenolytically in the presence of a hydrogenation catalyst, such aspalladium/carbon, in a suitable solvent, such as methanol, ethanol,ethanol/water, glacial acetic acid, ethyl acetate, dioxane ordimethylformamide, preferably at temperatures between 0° and 50° C., forexample at ambient temperature, and a hydrogen pressure of 1 to 5 bar.During the hydrogenolysis, other radicals may also be reduced at thesame time, for example a nitro group to the amino group, a benzyloxygroup to the hydroxy group, a vinylidene group to the correspondingalkylidene group or a cinnamic acid group to the correspondingphenylpropionic acid group, or may be replaced by hydrogen atoms, forexample a halogen atom may be replaced by a hydrogen atom.

If R₄ ' denotes a phthalimino group, this group may be convertedparticularly advantageously to an amino group, in the presence of aprimary organic base, such as methylamine, ethylamine or propylamine, ina suitable solvent, such as methanol, ethanol, isopropanol,dimethylformamide, methanol/dimethylformamide or methanol/water, bytransamidation at temperatures between 0° and 50° C., but preferably atambient temperature. If R₁ and/or R₂ denote here one of the iminoradicals mentioned hereinbefore, they are similarly converted to acorresponding amino group.

If R₁ and/or R₂ in a compound of formula VI represents one of theabove-mentioned imino groups, this may also be partially hydrolysedduring the reaction, for example into a 2-carboxyphenylcarbonylamino,20carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, whilst a methylene group ina 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted by one ortwo alkyl groups, and additionally the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, the substituentsbeing identical or different, and at the same time they may be wholly orpartially hydrogenated, a bicycloalkane-3-carboxylic acid amino orbicycloalkene-3-carboxylic acid amino group substituted by a carboxygroup in the 2-position, wherein the bicycloalkane and bicycloalkenemoieties each contain 9 or 10 carbon atoms, may be substituted by 1, 2or 3 methyl groups and an endomethylene group may be replaced by anoxygen atom, a 3-carboxy-n-propylenecarbonyl group wherein then-propylene group may be perfluorinated, substituted by one or two alkylgroups or substituted by a tetramethylene or pentamethylene group.

e) Reaction of a benzimidazole of the formula ##STR11## in which R₁ toR₃ are as hereinbefore defined, with a biphenyl compound of the formula##STR12## in which R₄ to R₆ are as hereinbefore defined, and

Z₃ is a nucleophilic leaving group, such as a halogen atom, for examplea chlorine, bromine or iodine atom, or a substituted sulphonyloxy group,for example a methanesulphonyloxy, phenylsulphonyloxy orp-toluenesulphonyloxy group.

The reaction is advantageously carried out in a solvent or solventmixture, such as methylene chloride, diethylether, tetrahydrofuran,dioxane, dimethylsulphoxide or benzene, optionally in the presence of anacid-binding agent, such as sodium carbonate, potassium carbonate,sodium hydroxide, potassium tert.butoxide, triethylamine or pyridine,wherein the two latter agents may also be used at the same time assolvent, preferably at temperatures between 0° and 100° C., for exampleat temperatures between ambient temperature and 50° C.

During the reaction, a mixture of the 1-isomer and 3-isomer ispreferably obtained.

f) For the preparation of a compound of the formula I, in which R₄ is a1-H-tetrazolyl group:

Cleaving a protective radical from a compound of the formula ##STR13##in which R₁ to R₃, R₃ and R₄ are as hereinbefore defined, and R₄ " is a1H-tetrazolyl group protected in the 1 position by a protective radical.

Suitable examples of a protective radical are the triphenylmethyl,tributyltin or triphenyltin group.

Cleaving a protective radical used is preferably carried out in thepresence of a hydrogen halide, preferably in the presence of hydrogenchloride, in the presence of a base, such as sodium hydroxide oralcoholic ammonia, in a suitable solvent, such as methylene chloride,methanol, methanol/ammonia, ethanol or isopropanol, at temperaturesbetween 0° and 100° C., but preferably at ambient temperature, or evenat elevated temperatures, if the reaction is carried out in the presenceof alcoholic ammonia, for example at temperatures between 100° and 150°C., preferably at temperatures between 120° and 140° C.

g) For the preparation of a compound of formula I, in which R₄ is a1H-tetrazolyl group:

Reaction of a compound of the formula ##STR14## (in which R₁ to R₃, R₃and R₄ are hereinbefore as defined with hydrazoic acid.

The reaction is preferably carried out in a solvent, such as benzene,toluene or dimethylformamide, at temperatures between 80° and 130° C.,preferably at 125° C. The hydrazoic acid is thus particularlyadvantageously released during the reaction from an alkali azide, forexample from sodium azide, in the presence of a weak acid, such asammonium chloride.

h) For the preparation of a compound of formula I, in which R₁ and/or R₂is an aminocarbonylamino group, which may be monosubstituted,disubstituted or trisubstituted by a bicyclic or tricyclic alkyl groupor by an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aralkylor aryl group, wherein a methylene group in a cycloalkyl radical having4 to 7 carbon atoms may be replaced by an oxygen atom:

Reaction of a compound of the formula ##STR15## (in which R₂ to R₄ areas hereinbefore defined, and

R₆ denotes a hydrogen atom, an alkyl group having 1 to 20 carbon atoms,an alkenyl or alkynyl group each having 3 to 5 carbon atoms, acycloalkyl group having 3 to 7 carbon atoms, a cycloalkylalkyl group, inwhich the cycloalkyl moiety may contain 3 to 7 carbon atoms, the alkylmoiety may contain 1 to 3 carbon atoms and in a cycloalkyl moiety having4 to 7 carbon atoms a methylene group may be replaced by an oxygen atom,a bicyclic or tricyclic alkyl group having 7 to 10 carbon atoms, an arylor aralkyl group having 1 to 3 carbon atoms in the alkyl moiety, whereinthe aryl group may be a phenyl group optionally substituted by afluorine, chlorine or bromine atom a hydroxy, alkyl or alkoxy group eachhaving 1 to 4 carbon atoms) with a compound of the formula ##STR16## inwhich R₉, which may be the same or different, have the meaningsmentioned above for R₉,

W is an oxygen or sulphur atom,

Z₄ is a nucleophilic leaving group, such as a chlorine or bromine atom,or also if at least one of the radicals R₁ is a hydrogen atom,

Z₄ and R₄ together are a nitrogen-carbon bond or a cycloalkyleneiminogroup having 4 to 6 carbon atoms, or a morpholino group.

The reaction is preferably carried out in a solvent, such astetrahydrofuran, dioxane, ethylene chloride or benzene, optionally inthe presence of an acid-binding agent, such as triethylamine orpyridine, advantageously at temperatures between 0° and 100° C.,preferably at temperatures between 20° and 80° C.

i) For the preparation of a compound of the formula I, in which R₄ is atrifluoromethylcarbonylamino, trifluoromethylcarbonylaminomethyl,trifluoroethylsulphonylamino, trifluoromethylsulphonylaminomethyl or1H-tetrazolyl group, an alkylcarbonylamino, alkylcarbonylaminomethyl,arylcarbonylamino, arylcarbonylaminomethyl, aralkylcarbonylamino,aralkylcarbonylaminomethyl, alkylsulphonylamino,alkylsulphonylaminomethyl, arylsulphonylamino, arylsulphonylaminomethyl,aralkylsulphonylamino or aralkylsulphonylaminomethyl group, in which thealkyl moiety may contain 1 to 3 carbon atoms in each case:

Acylation of a compound of the formula ##STR17## (in which R₁ to R₃, R₅ad R₆ are as hereinbefore defined, and

R₄ "' is an amino or aminomethyl group) using a compound of the formula

    HO--U--R.sub.10                                            (XIV)

in which

R₁₀ denotes a trifluoromethyl group, an alkyl, aryl or aralkyl group,wherein the alkyl moiety may contain 1 to 3 carbon atoms in each case,and

U denotes a carbonyl or sulphonyl group, or using reactive derivativesthereof, such as acid halides, acid esters or acid anhydrides.

Suitable examples of reactive derivatives of a compound of the formulaXIV are esters thereof, such as methyl, ethyl or benzyl esters,thioesters thereof, such as methylthio or ethylthio ester, halidesthereof, such as the acid chlorides, anhydrides or imidazolides thereof.

The reaction is advantageously carried out in a solvent or solventmixture, such as water, methylene chloride, chloroform, ether,tetrahydrofuran, dioxane or dimethylformamide, using a correspondingcarboxylic acid in the presence an acid activating or a dehydratingagent, such as thionyl chloride, using anhydrides thereof, such asacetic anhydride, using esters thereof, such as ethyl acetate, usinghalides thereof, such as acetyl chloride or methanesulphonyl chloride,optionally in the presence of an inorganic or tertiary organic base,such as sodium hydroxide, potassium carbonate, triethylamine orpyridine, wherein the two latter bases may also serve as solvent at thesame time, at temperatures between -25° and 100° C., but preferably attemperatures between -10° and 80° C.

k) For the preparation of a compound of the formula I, in which R₄ is analkylsulphonylaminocarbonyl or perfluoroalkylsulphonylamino group eachhaving 1 to 4 carbon atoms in the alkyl moiety, or is abenzylsulphonylaminocarbonyl group:

Reaction of a reactive derivative of a carboxylic acid of the formula##STR18## in which R₁ to R₃, R₅ and R₆ are as hereinbefore defined, witha sulphonamide of the formula

    H.sub.2 N--SO.sub.2 --R.sub.11                             (XVI)

in which

R₁₁ is an alkyl or perfluoroalkyl group each having 1 to 4 carbon atoms,or is a benzyl group, or with alkali metal salt thereof.

Suitable reactive derivatives of a carboxylic acid of the formula XV,which may be prepared in the reaction mixture, are halides thereof, suchas the chloride or bromide, or carbonate derivatives thereof, such asthe imidazolcarbonyloxy or diphenylcarbamoyloxy derivative.

The reaction is advantageously carried out in a suitable solvent, suchas methylene chloride, tetrahydrofuran, dioxane or dimethylsulphoxide,at temperatures between 0° and 180° C., preferably between ambienttemperature and 150° C. However, the reaction may also be carried out ina melt.

l) For the preparation of a compound of the formula I, in which R₂ is a2-imidazolidon-1-yl or 3,4,5,6-tetrahydro-2-pyrimidon-1-yl groupoptionally substituted in the 3 position by an alkyl, cycloalkyl,cycloalkylalkyl or aralkyl group:

Cyclisation of a compound of the formula ##STR19## (in which R₁, R₃ andR₄ to R₆ are as hereinbefore defined, Hal is a chlorine, bromine oriodine atom, and n is the number 2 or 3) and, if required, subsequentreaction with a compound of the formula

    R.sub.12 --Hal                                             (XVIII)

in which

R₁₂ is an alkyl, cycloalkyl, cycloalkylalkyl or aralkyl group, and

Hal is a chlorine, bromine or iodine atom.

Cyclisation and, if required, the subsequent alkylation, isadvantageously carried out in a solvent, such as methanol, ethanol,benzene or dimethylsulphoxide, optionally in the presence of a phasetransfer catalyst, such as benzyltriethylammonium bromide, in thepresence of an acid-binding agent, such as sodium hydroxide, sodiummethoxide, sodium ethoxide, sodium hydride or potassium tert.butoxide,at temperatures between 20° and 100° C., preferably at temperaturesbetween 30° and 70° C.

m) For the preparation of compounds of the general formula I, in which

R₁ denotes an amino group, which is monosubstituted by adialkylaminoalkanoyl, acyl, cycloalkoxycarbonyl,cycloalkylalkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl ortrifluoroacetyl group, by an alkylsulphonyl group having 1 to 4 carbonatoms, by an alkoxycarbonyl group having a total of 2 to 7 carbon atoms,or by a thiazolidin-3-ylcarbonyl group substituted by an alkoxycarbonylgroup,

an alkylamino group having 1 to 6 carbon atoms, which may be substitutedat the nitrogen atom by an alkylsulphonyl or acyl group, wherein, if theacyl group is an alkanoyl group, it may additionally be substituted byan alkoxy group, and the alkyl substituent may be substituted atposition 2 by a hydroxy, alkoxy or arylamino group,

an N-alkoxycarbonyl-alkylamino, N-cycloalkoxycarbonylalkylamino,N-cycloalkylalkoxycarbonyl-alkylamino, N-aryloxycarbonyl-alkylamino orN-aralkoxycarbonyl-alkylamino group, in which the alkyl group maycontain 1 to 6 carbon atoms in each case, an alkoxycarbonylamino,cycloalkoxycarbonylamino, cycloalkylalkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, acylamino oralkylsulphonylamino group substituted at the nitrogen atom by acycloalkyl, cycloalkylalkyl or aralkyl group, or

a phthalimino, homophthalimino, 2-carboxyphenylcarbonylamino,2-carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, whilst a carbonyl group ina phthalimino group may be replaced by a methylene group and a methylenegroup in a homophthalimino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted b one ortwo alkyl groups, and additionally the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, whilst thesubstituents may be identical or different, and at the same time theymay be partially or wholly hydrogenated, a bicycloalkane-3-carboxylicacid amino or bicycloalkene-3-carboxylic acid amino group substituted bya carboxy group in the 2-position, a bicycloalkane-2,3-dicarboxylic acidimino or bicycloalkane-2,3-dicarboxylic acid imino group, wherein thebicycloalkane and bicycloalkene parts each contain 9 or 10 carbon atoms,may be substituted by 1, 2 or 3 methyl groups and an endomethylene groupmay be replaced by an oxygen atom, a glutaric acid imino or3-carboxy-n-propylene-carbonyl group wherein the n-propylene group maybe perfluorinated, substituted by one or two alkyl groups or by atetramethylene or pentamethylene group, and

R₄ has the meanings mentioned hereinbefore for R₄, with the exception ofthe amino group:

Acylation of a compound of the general formula ##STR20## (in which R₂,R₄, R₅ and R₆ are as hereinbefore defined,

R₄ is as hereinbefore defined, with the exception of the amino group,and

R₁₃ denotes a hydrogen atom, an alkyl group having 1 to 6 carbon atoms,which may be substituted at position 2 by a hydroxy, alkoxy or arylaminogroup, a cycloalkyl, cycloalkylalkyl or aralkyl group) using a compoundof the formula

    R.sub.14 --Z.sub.5                                         (XX)

(in which

R₁₄ denotes a dialkylaminoalkanoyl, cycloalkoxycarbonyl,cycloalkylalkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl ortrifluoroacetyl group, an alkylsulphonyl group having 1 to 4 carbonatoms, an alkoxycarbonyl group having a total of 2 to 7 carbon atoms, athiazolidin-3-ylcarbonyl group substituted by an alkoxycarbonyl group,or an acyl group, in which, if the acyl group is an alkanoyl group, itmay additionally be substituted by an alkoxy group, or a2-carboxyphenylcarbonyl, 2-carboxyphenylmethyl,2-carboxyphenylmethylenecarbonyl or 2-carboxymethylenephenylcarbonylgroup, whilst a methylene group in a 2-carboxyphenylmethylenecarbonyl or2-carboxymethylenephenylcarbonyl group may be substituted by one or twoalkyl groups, and in addition the above-mentioned phenyl nuclei may bemono- or disubstituted by alkyl or alkoxy groups, the substituent beingidentical or different, and at the same time they may be wholly orpartially hydrogenated, a bicycloalkane-3-carbonyl orbicycloalkene-3-carbonyl groups substituted in the 2-position by acarboxy group, wherein the bicycloalkane and bicycloalkene moieties eachcontain 9 or 10 carbon atoms, may be substituted by 1, 2 or 3 methylgroups and an endomethylene group may be replaced by an oxygen atom, a3-carboxy-n-propylenecarbonyl group wherein the n-propylene group may beperfluorinated, substituted by one or two alkyl groups or by atetramethylene or pentamethylene group, and

Z₅ denotes a nucleophilic leaving group) or reactive derivativesthereof, such as acid halides, acid esters or acid anhydrides.

Suitable examples of reactive derivatives of a compound of the formulaXIX are esters thereof, such as methyl, ethyl or benzyl esters;thioesters thereof, such as methylthio or ethylthio esters; halidesthereof, such as acid chlorides, anhydrides or imidazolides thereof.

The reaction is advantageously carried out in a solvent or solventmixture, such as water, methylene chloride, chloroform, ether,tetrahydrofuran, dioxane or dimethylformamide, using a correspondingcarboxylic acid in the presence of an acid activating or dehydratingagent, such as thionyl chloride, using anhydrides thereof, such asacetic anhydride, using esters thereof, such as ethyl acetate, usinghalides thereof, such as acetyl chloride or methanesulphonyl chloride,optionally in the presence of an inorganic or tertiary organic base,such as sodium hydroxide, potassium carbonate, triethylamine orpyridine, wherein the two latter bases may also serve as solvent at thesame time, at temperatures between -25° and 100° C., but preferably attemperatures between -10° and 80° C.

n) In order to prepare compounds of general formula I wherein at leastone of the groups R₁ or R₂ represents a 2-carboxyphenylcarbonylamino,2-carboxyphenylmethylamino, 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group, where a methylene groups ina 2-carboxyphenylmethylenecarbonylamino or2-carboxymethylenephenylcarbonylamino group may be substituted by one ortwo alkyl groups, and in addition the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, whilst thesubstituents may be identical or different, and at the same time may bewholly or partially hydrogenated, a bicycloalkane-3-carboxylic acidamino or bicycloalkene-3-carboxylic acid amino group substituted by acarboxy group in the 2-position, wherein the bicycloalkane andbicycloalkene moieties each contain 9 or 10 carbon atoms, may besubstituted by 1, 2 or 3 methyl groups and an endomethylene group may bereplaced by an oxygen atom, a 3-carboxy-n-propylenecarbonyl groupwherein the n-propylene group may be perfluorinated, substituted by oneor two alkyl groups or by a tetramethylene or pentamethylene group:

Partial hydrolysis of a compound of general formula ##STR21## wherein R₂to R₆ are defined as hereinbefore and

R₁₅ represents a phthalimino or homophthalimino group, whilst a carbonylgroup in a phthalimino group may be replaced by a methylene group and amethylene group in a homophthalimino group may be substituted by one ortwo alkyl groups, and in addition the above-mentioned phenyl nuclei maybe mono- or disubstituted by alkyl or alkoxy groups, the substituentsbeing identical or different, and at the same time may be wholly orpartially hydrogenated, a bicycloalkane-2,3-dicarboxylic acid imino orbicycloalkene-2,3-dicarboxylic acid imino group wherein thebicycloalkane and bicycloalkane moieties each contain 9 or 10 carbonatoms, may be substituted by 1, 2 or 3 methyl groups and anendomethylene group may be replaced by an oxygen atom, a glutaric acidimino group wherein the n-propylene group may be perfluorinated,substituted by one or two alkyl groups or by a tetramethylene orpentamethylene group.

Partial hydrolysis is expediently carried out either in the presence ofan acid such as hydrochloric, sulphuric, phosphoric, trichloroacetic ortrifluoroacetic acid or in the presence of a base such as sodiumhydroxide or potassium hydroxide in a suitable solvent such as water,water/methanol, ethanol, water/ethanol, water/isopropanol orwater/dioxan at temperatures between -10° C. and 120° C., e.g. attemperatures between ambient temperature and the boiling temperature ofthe reaction mixture. However, it is particularly advantageous to carryout the partial hydrolysis in the presence of one equivalent of aninorganic base at ambient temperature.

In the reactions described above, optionally present reactive groups,such as hydroxy, amino or alkylamino groups may be protected during thereaction by conventional protective groups, which are cleaved againafter the reaction.

Suitable examples of a protective radical for a hydroxy group are thetrimethylsilyl, acetyl, benzoyl, methyl, ethyl, tert.butyl, benzyl ortetrahydropyranyl group, and of protective radicals for an amino,alkylamino or imino group are acetyl, benzoyl, ethoxycarbonyl or benzylgroups.

The optional subsequent cleaving of a protective group used ispreferably carried out hydrolytically in an aqueous solvent, for examplein water, isopropanol/water, tetrahydrofuran/water or dioxane/water, inthe presence of an acid, such as hydrochloric acid or sulphuric acid, orin the presence of an alkali metal base, such as sodium hydroxide orpotassium hydroxide, at temperatures between 0° and 100° C., preferablyat the boiling temperature of the reaction mixture. However, cleaving abenzyl radical is preferably carried out hydrogenolytically, for examplewith hydrogen in the presence of a catalyst, such as palladium/carbon,in a solvent, such as methanol, ethanol, ethyl acetate or glacial aceticacid, optionally with addition of an acid, such as hydrochloric acid, attemperatures between 0° and 50° C., but preferably at ambienttemperature, and a hydrogen pressure of 1 to 7 bar, but preferably 3 to5 bar.

If a compound of the formula I in which R₁ and/or R₂ is a nitro group isobtained in accordance with the invention, it may be converted to acorresponding amino compound of the formula I by means of reduction, or

if a compound of the formula I in which R₁ and/or R₂ is a hydroxy,amino, alkylamino, phenylalkylamino, alkylsulphonylamino or acylaminogroup is obtained in accordance with the invention, it may be convertedto a corresponding alkylated compound of the formula I by means ofalkylation, or

if a compound of the formula I in which R₁ and/or R₂ is a benzyloxygroup is obtained in accordance with the invention, it may be convertedto a corresponding compound of the formula I, in which R₁ and/or R₂ is ahydroxy group, by means of debenzylation, or

if a compound of the formula I in which R₁ and/or R₂ is a carboxy groupis obtained in accordance with the invention, it may be converted to acorresponding compound of the formula I, in which R₁ and/or R₂ is anaminocarbonyl group optionally substituted by one or two alkyl groupseach having 1 to 3 carbon atoms, by means of amidation, or

if a compound of the formula I in which R₁ and/or R₂ is a carboxy groupand/or R₄ is a cyano group is obtained in accordance with the invention,it may be converted to a corresponding compound of the formula I, inwhich R₁ and/or R₂ is a hydroxymethyl group and/or R₄ is an aminomethylgroup, by means of reduction, or

if a compound of the formula I in which R₁ and/or R₂ is analkoxycarbonyl group is obtained in accordance with the invention, itmay be converted in accordance with the invention to a correspondingcompound of the formula I, in which R₁ and/or R₂ is a carboxy group, bymeans of hydrolysis, or

if a compound of the formula I in which R₁ and/or R₂ is an alkoxy orphenylalkoxy group is obtained in accordance with the invention, it maybe converted to a corresponding compound of the formula I, in which R₁and/or R₂ is a hydroxy group, by means of ether cleaving, or

if a compound of the formula I, in which R₁ and/or R₂ is anaminocarbonylamino or aminothiocarbonyl group, which is substituted by acycloalkyl group having 5 to 10 carbon atoms, in which a methylene groupis replaced in the 2 position by an oxygen atom, and which may beadditionally monosubstituted or disubstituted by an alkyl group having 1to 20 carbon atoms, by an alkenyl or alkynyl group each having 3 to 5carbon atoms, by a bicyclic or tricyclic alkyl group having 7 to 11carbon atoms, by a cycloalkyl, cycloalkylalkyl, aralkyl or aryl group,is obtained in accordance with the invention, it may be converted to acorresponding compound of the formula I, in which R₁ and/or R₂ is anaminocarbonylamino or aminothiocarbonyl group, which is substituted by a4-hydroxy-n-butyl, 5-hydroxy-n-pentyl or 6-hydroxy-n-hexyl group and mayadditionally be monosubstituted or disubstituted by an alkyl grouphaving 1 to 20 carbon atoms, by an alkenyl or alkynyl group each having3 to 5 carbon atoms, by a bicyclic or tricyclic alkyl group having 7 to11 carbon atoms, by a cycloalkyl, cycloalkylalkyl, aralkyl or arylgroup, by means of reduction, or

if a compound of the formula I, in which R₁ and/or R₂ is a phthaliminogroup, which may be monosubstituted or disubstituted by an alkyl oralkoxy group, wherein the substituents may be the same or different, isobtained in accordance with the invention, it may be converted to acorresponding compound of the formula I, in which R₁ and/or R₂ is a1-oxo-isoindolin-2-yl group, which may be monosubstituted ordisubstituted by an alkyl or alkoxy group, wherein the substituents maybe the same or different, by means of reduction, or

a resulting 1 and 3 isomer mixture of a compound of the formula I may beseparated into its 1 isomer and 3 isomer by means of isomer separation.

The subsequent reduction of the nitro group is preferably carried out ina solvent, such as water, water/ethanol, methanol, glacial acetic acid,ethyl acetate or dimethylformamide, advantageously using hydrogen in thepresence of a hydrogenation catalyst, such as Raney nickel, platinum orpalladium/carbon, using metals, such as iron, tin or zinc, in thepresence of an acid, using salts, such as iron (II) sulphate, tin (II)chloride, sodium sulphide, sodium hydrogen sulphite or sodiumdithionite, or using hydrazine in the presence of Raney nickel, attemperatures between 0° and 80° C., but preferably at temperaturesbetween 20° and 40° C.

The subsequent alkylation is preferably carried out in a solvent orsolvent mixture, such as methylformamide, dimethylformamide,dimethylsulphoxide, benzene, chlorobenzene, tetrahydrofuran,benzene/tetrahydrofuran or dioxane, in the presence of an alkylatingagent, such as methyliodide, methylbromide, ethylbromide,dimethylsulphate, benzylchloride or diazomethane, optionally preferablyin the presence of an acid-binding agent, for example an alkoxide suchas potassium tert.butoxide, an alkali metal hydroxide, such as sodiumhydroxide or potassium hydroxide, an alkali metal carbonate, such aspotassium carbonate, an alkali metal amide, such as sodium amide, or analkali metal hydride, such as sodium hydride, advantageously attemperatures between 0° and 150° C., preferably at temperatures between0° and 50° C.

The subsequent reductive amination of an amino group is carried out in asuitable solvent, such as methanol, ethanol, tetrahydrofuran, dioxane oracetonitrile, in the presence of a suitable reducing agent, such as asuitable complex metal hydride, but preferably in the presence of sodiumcyanoborohydride, at a pH of 5 to 7, at temperatures between 0° and 50°C., but preferably at ambient temperature.

The subsequent cleaving of a benzyl radical is preferably carried outhydrogenolytically, for example using hydrogen in the presence of acatalyst, such as palladium/carbon, in a solvent, such as methanol,ethanol, ethyl acetate or glacial acetic acid, optionally with additionof an acid, such as hydrochloric acid, at temperatures between 0° and50° C., but preferably at ambient temperature, and a hydrogen pressureof 1 to 7 bar, but preferably 3 to 5 bar.

The subsequent amidation is advantageously carried out in a solvent,such as methylene chloride, chloroform, carbon tetrachloride, ether,tetrahydrofuran, dioxane, benzene, toluene, acetonitrile ordimethylformamide, but particularly advantageously in an excess of theamine used, for example in methanol, ethanol, n-propanol, isopropanol,ammonia, methylamine, ethylamine, dimethylamine or diethylamine,optionally in the presence of an acid activating agent or a dehydratingagent, for example in the presence of ethyl chloroformate, thionylchloride, phosphorus trichloride, phosphorus pentoxide,N,N'-dicyclohexylcarbodiimide,N,N'-dicyclohexylcarbodiimide/N-hydroxysuccinimide,N,N'-carbonyldiimidazole or N,N'-thionyldiimidazole ortriphenylphosphine/carbon tetrachloride, or an agent activating theamino group, for example phosphorus trichloride, and optionally in thepresence of an inorganic base, such as sodium carbonate, or a tertiaryorganic base, such as triethylamine or pyridine, which may serve assolvent at the same time, at temperatures between -25° C. and 250° C.,but preferably at temperatures between -10° C. and the boilingtemperature of the solvent used.

The subsequent reduction of the carboxy group is carried out in asuitable solvent, such as methanol, ethanol ether, tetrahydrofuran,dioxane or glacial acetic acid, in the presence of catalyticallyactivated hydrogen, for example hydrogen in the presence of platinum orpalladium/carbon, and optionally in the presence of an acid, such ashydrochloric acid or perchloric acid, or in the presence of a metalhydride, such as sodium borohydride, lithium borohydride or lithiumaluminium hydride, at temperatures between 0° and 100° C., preferably attemperatures between 20° and 80° C.

The subsequent hydrolysis is preferably carried out hydrolytically in anaqueous solvent, for example in water, isopropanol/water,tetrahydrofuran/water or dioxane/water, in the presence of an acid, suchas hydrochloric acid or sulphuric acid, or in the presence of an alkalimetal base, such as sodium hydroxide or potassium hydroxide, attemperatures between 0° and 100° C., preferably at the boilingtemperature of the reaction mixture.

The subsequent ether cleaving is carried out in the presence of an acid,such as hydrogen chloride, hydrogen bromide, sulphuric acid, borontrichloride, boron tribromide or aluminium chloride, in a suitablesolvent, such as methanol, ethanol, water/isopropanol, methylenechloride, chloroform or carbon tetrachloride, at temperatures between-30° C. and the boiling temperature of the reaction mixture.

The subsequent reduction if preferably carried out in a solvent, such aswater, water/ethanol, methanol, glacial acetic acid, ethyl acetate ordimethylformamide, advantageously using hydrogen in the presence of ahydrogenation catalyst, such as Raney nickel, platinum orpalladium/carbon, or using hydrazine in the presence of Raney nickel, attemperatures between 0° and 50° C., but preferably at ambienttemperature.

The subsequent reduction of a phthalimino group is preferably carriedout in a solvent, such as glacial acetic acid using nascent hydrogen,for example using zinc/glacial acetic acid, at temperatures between 80°and 120° C., preferably at the boiling temperature of the reactionmixture.

The subsequent isomer separation is preferably carried outchromatographically using a carrier, such as silica gel or aluminiumoxide.

Furthermore, the compounds of the formula X obtained may be converted totheir acid addition salts, in particular for the pharmaceuticalapplication, to their physiologically acceptable salts, using inorganicor organic acids. Examples of acids suitable for this purpose arehydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid,fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid ormaleic acid.

In addition, the novel compounds of the formula I thus obtained, if theycontain a carboxy group, can then be converted, if desired to theiraddition salts using inorganic or organic bases, in particular for thepharmaceutical application, to their physiologically acceptable additionsalts. Examples of bases suitable for this purpose are sodium hydroxide,potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine andtriethanolamine.

Some of the compounds of the formulae II to XXI used as startingmaterials are known in the literature or they are obtained by processesknown in the literature.

Thus for example a compound of the formula II or III is obtained byalkylating a corresponding o-amino-nitro compound and subsequentlyreducing the nitro group.

A compound of the formulae V, VI, VII, IX, X, XI, XIII, XV, XVII, XIX orXXI used as starting material is obtained by alkylating a correspondingo-phenylenediamine or a corresponding o-amino-nitro compound andsubsequently reducing the nitro group and subsequently cyclising ano-diaminophenyl compound thus obtained, or by NH-alkylating acorresponding 1H-benzimidazole, wherein the isomer mixture thus obtainedmay then be separated by means of conventional methods, for example bymeans of chromatography.

The novel compounds of the formula I and their physiologicallyacceptable addition salts have valuable pharmacological properties. Inparticular, they are angiotensin II antagonists.

By way of example, the compounds

A=4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

B=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

C=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-ethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

D=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-propyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

E=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

F=4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate,

G=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-pentyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

H=4'-(2-n-butyl-6-(N-methylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

I=4'-(2-n-butyl-6-(1-oxo-isoindolin-2-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate,

J=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

K=4'-(2-n-butyl-6-n-pentanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

L=4'-(2-n-butyl-6-propionylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

M=4'-(2-n-butyl-6-isopropylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

N=4'-(2-n-butyl-6-(tetrahydropyran-2-yl-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

O=4'-(2-n-butyl-6-(n-butylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

P=4'-(6-n-butanoylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

Q=4'-(2-n-butyl-6-(N-ethoxycarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

R=4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate,

S=4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

T=4'-(2-n-butyl-6-((5-hydroxy-n-pentyl)-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid monohydrate,

U=4'-(2-n-butyl-6-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

V=4'-(2-n-butyl-6-cyclohexylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

W=4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid,

X=4'-(2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenylhydrate,

Y=4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate,

Z=4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid,

AA=4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

BB=4'-(2-n-butyl-6-cyclopentylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semihydrate

CC=4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

were investigated for their biological effects as follows:

a) rats (male, 180-220 g) are anaesthetised using sodium hexobarbital(150 mg/kg i.p.). After the anaesthetic has taken effect, a trachealcannula is inserted, the spine is destroyed in the animals and then theyare immediately respirated artifically using a respiratory pump. Thearterial blood pressure is recorded via a cannula in the carotid arteryby means of a Bell & Howell pressure sensor. Substances are administeredvia a cannula in the jugular vein.

Test substances are administered in three doses (10, 20 and 30 mg/kgi.v.), wherein one dose of substance is tested per animal. Three minutesafter intravenous administration of the test substance, angiotensin IIis administered intravenously in increasing doses, and hence acumulative dose-effect relationship is established for angiotensin II inthe presence of the test substances. The measured parameter is theincrease in the arterial blood pressure.

These dose-effect graphs are compared with standard graphs forangiotensin II without test substances. A computer program determinesthe displacements to the right of the dose-effect graphs for angiotensinII as a result of test substances, and calculates corresponding pA₂values for the test substances.

The following table shows the average pA₂ values of the substancesinvestigated:

    ______________________________________    Substances    pA.sub.2 values    ______________________________________    A             7, 23    B             6, 63    C             6, 36    D             6, 59    E             7, 34    F             7, 56    G             6, 89    H             6, 48    I             6, 12    J             7, 38    K             6, 38    L             6, 04    M             6, 87    N             7, 02    O             6, 46    P             6, 46    Q             6, 83    R             7, 16    S             6, 69    T             7, 20    V             7, 26    W             6, 28    X             6, 57    Y             6, 97    Z             7, 15    AA            --    BB            --    CC            8, 54    ______________________________________

b) The inhibiting effect of the novel compounds on the bonding ofangiotensin II to bovine adrenal gland receptor preparations was testedanalogously to the method of Glossmann et al. (J. Biol. Chem. 249,825-834 (1974). The incubation batch contained aliquots of a membranepreparation of bovine adrenal cortex in tris buffer, increasingconcentrations of the possible antagonists and 50 pM ¹²⁵ I-angiotensinII. After 45 minutes the incubation was stopped by rapid filtrationthrough glass fibre filters. The radioactivity associated with thefilter was determined in a γ-counter at a counting efficiency of 80%.

The following table shows the inhibitor concentration of the antagonistswhich effected 50% inhibition of the specific ¹²⁵ I-angiotensin IIbonding:

    ______________________________________    Substances    IC.sub.50  nM/l!    ______________________________________    A             29    B             29    C             31    D             44    E             46    F             47    G             46    H             51    I             51    J             54    K             57    L             58    M             61    N             65    O             65    P             67    Q             68    R             72    S             72    T             76    U             79    V             84    W             86    X             99    Y             150    Z             133    AA            100    BB            46    CC            1000    ______________________________________

Furthermore, no toxic side effects could be observed for theadministration of the above compounds up to a dose of 30 mg/kg i.v., forexample no negative inotropic effect and no cardiac rythmn disorders.Accordingly, the compounds are well tolerated.

The novel compounds and their physiologically acceptable addition saltsdue to their pharmacological properties, are suitable for the treatmentof hypertonia and cardiac insufficiency, also for the treatment ofischaemic peripheral circulatory disorders, myocardial ischaemia(Angina), for the prevention of cardiac insufficiency progression aftermyocardial infarction, for the treatment of diabetic nephropathy,glaucoma, gastrointestinal illnesses and diseases of the bladder.

The dosage required to achieve a corresponding effect is conveniently 20to 100 mg for intravenous administration, preferably 30 to 70 mg, and 50to 200 mg for oral administration, preferably 75 to 150 mg, 1 to 3×dailyin each case. The compounds of the formula I prepared in accordance withthe invention can be formulated for this purpose, optionally incombination with other active ingredients, together with one or moreinert conventional excipients and/or diluents, for example with cornstarch, lactose, cane sugar, microcrystalline cellulose, magnesiumstearate, polyvinylpyrrolidone, citric acid, tartaric acid, water,water/ethanol, water/glycerol, water/sorbitol, water/polyethyleneglycol, propylene glycol, cetylstearyl alcohol, carboxymethylcelluloseor fat-containing substances, such as hard fat or suitable mixturesthereof, in conventional galenic preparations, such as tablets, coatedtablets, capsules, powders, suspensions or suppositories.

The following Examples should illustrate the invention in more detail:

EXAMPLE A Tert.butyl 4'N-(5-benzylamino-2-nitrophenyl)-pentanoylaminomethyl!biphenyl-2-carboxylate

3.9 g (7.5 mmol) of tert.butyl 4'-N-(5-chloro-2-nitrophenyl)-pentanoylaminomethyl!biphenyl-2-carboxylateare stirred together with 3.9 ml of benzylamine for 3 hours in an oilbath heated at 150°-160° C. After cooling the reaction mixture, theresidue is dissolved in about 25 ml of methylene chloride and thesubstance is purified over a silica gel column (grain size: 0.063-0.2mm, eluting agent: cyclohexane/5-10% ethyl acetate). The appropriatefractions are evaporated on a rotary evaporator.

Yield: 2.9 g (65.5% of theoretical),

Oil, R_(f) value: 0.55 (Silica gel: cyclohexane/ethyl acetate=2:1).

The following compounds are obtained in analogous manner:

tert.butyl 4'-N-(5-(N-benzyl-methylamino)-2-nitrophenyl)-pentanoylaminomethyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Silica gel: cyclohexane/ethyl acetate=4:1).

tert.butyl 4'-N-(5-dimethylamino-2-nitrophenyl)-pentanoylaminomethyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (Silica gel: hexane/ethyl acetate=4:1).

EXAMPLE 1 Tert.butyl 4'-(benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

0.95 g (8 mmol) of benzimidazole are dissolved in 50 ml ofdimethylsulphoxide and treated with 1.0 g (9 mmol) of potassiumtert.butoxide. To form the salt, the mixture is then stirred for 30minutes at ambient temperature and 2.8 g (8 mmol) of tert.butyl4'-bromomethyl-biphenyl-2-carboxylate are then added. The reaction iscompleted after stirring for 2 hours at ambient temperature. The mixtureis diluted to 500 ml using water and extracted 3 times using about 100ml of ethyl acetate. The combined organic phases are dried usingmagnesium sulphate and evaporated to dryness. The oily residue ispurified over a silica gel column (grain size: 0.063-0.2 mm), methylenechloride with 1% ethanol being used as eluting agent. The homogeneousfractions are evaporated to dryness. The residue is an oil.

Yield: 2.8 g (90.8% of theoretical),

R_(f) value: 0.35 (Silica gel: methylene chloride/ethanol=19:1)

Calculated: C 78.10 H 6.29 N 7.29 Found: 78.18 6.34 7.19

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.15 (Silica gel: methylene chloride/ethanol=49:1)

tert.butyl 4'-(2-n-butyl-7-(2-diethylamino-ethoxy)-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: methylene chloride/ethanol=9:1)

tert.butyl 4'-(2-ethylthio-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil,R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=49:1)

tert.butyl 4'-(2-n-propylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-methyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil, R_(f)value: 0.60 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-methylmercapto-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.55 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-methyl-5- and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-methyl-5- and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.60 (Silica gel: methylene chloride/ethanol=9:1)

tert.butyl 4'-(2-(2-methylpropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1.1)

tert.butyl 4'-(2-methoxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-(pyrid-2-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.40 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (5- and6-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.25 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-phenyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil, R_(f)value: 0.45 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(thiazol-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.30 (Silica gel: methylene chloride/ethanol=49:1)

tert.butyl 4'-(2-(3,5-dimethyl-pyrazol-1-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(fur-2-yl)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil,R_(f) value: 0.40 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-aminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-isopropyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil,R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-hydroxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.35 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(3-hydroxypropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-methyl-5- and6-(N-(methoxyacetyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(1-methylpropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.80 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-(2-methylbutyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.60 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'- (2-methyl-5- and6-(N-(2-methoxyethyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.25 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-pentyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil, R_(f)value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-7-methoxy-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-propyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate meltingpoint: 140°-141° C.

tert.butyl 4'-(2-ethyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate meltingpoint: 129°-130° C.

tert.butyl 4'-(2-ethylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-methylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-chloro-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate oil, R_(f)value: 0.55 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.55 (Silica gel: methylene chloride/ethanol=49:1)

tert.butyl 4'-(2-(4-methoxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.80 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-propylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=49:1)

tert.butyl 4'-(2-n-butylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-(4-methoxyphenyl)-5- and6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'- (2-n-butyl-5- and6-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.60 (Silica gel: ethyl acetate/ethanol/ammonia=90:10:1)

tert.butyl 4'- (2-n-butyl-5- and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.80 (Silica gel: ethyl acetate/ethanol/ammonia=90:10:1)

tert.butyl 4'- (2-n-butyl-5- and6-methoxy-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.70 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(7-n-butoxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(4-hydroxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 258°-260° C.

tert.butyl 4'-(2-(4-n-butoxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-4-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(3-pyridyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.40 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-(4-benzyloxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.75 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(2,2-dimethylpropyl)-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.48 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-benzyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.52 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(2-methylbutyl)-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-cyclohexylmethyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.52 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-cyclohexylmethyl-5,6-dichloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.46 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-(2-methylbutyl)-naphtho2,3-d!imidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f) value:0.57 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-n-propyl-naphtho2,3-d!imidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f) value:0.57 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-5,6-dichloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-cyclohexylmethyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.47 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.46 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-cyclopentylmethyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.47 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(3-methylbutyl)-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.47 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-cyclohexyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-(1-butyn-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.49 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-6-ethoxycarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: petroleum ether/ethyl acetate=1:1+1%glacial acetic acid)

tert.butyl 4'-(2-cyclopentyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-n-butyl-5- and6-fluoro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.25 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'- (2-n-butyl-5- and6-benzoyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.28 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'- (2-n-butyl-5- and6-trifluoromethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.33 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'-(2-n-butyl-4-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-n-butyl-5- and6-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.30 (Silica gel: methylene chloride/methanol/aceticacid=19:0.8:0.2)

tert.butyl 4'-(2-n-butyl-6-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.90 (Silica gel: methylene chloride/methanol/aceticacid=9:0.8:0.2)

tert.butyl 4'-(2-n-butyl-5-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 224°-225° C.

tert.butyl 4'-(2-n-butyl-6-aminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 159°-160° C.

tert.butyl 4'-(2-n-butyl-5-aminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 135°-138° C. (decomposition)

tert.butyl 4'- (2-n-butyl-5- and6-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.50 (Silica gel: methylene chloride/ethanol=100:1)

tert.butyl 4'-(2-n-butyl-6-(1H-tetrazol-5-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: from 115° C. (decomposition)

tert.butyl 4'- (2-n-butyl-5- and6-(1H-tetrazol-5-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: from 92° C. (decomposition)

4'-(2-n-butyl-6-(cis-hexahydrophthalinino)-benzimidazol-1-yl)-methyl!-1-cyano-2-phenylnaphthalene

tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-2-phenylnaphthalene-1-carboxylateoil, R_(f) value: 0.25 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-phenylnaphthalene-1-carboxylate

tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylateoil, R_(f) value: 0.43 (Silica gel: ethyl acetate/petroleum ether=2:1)

tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylateoil, R_(f) value: 0.35 (Silica gel: methylene chloride/ethanol=50:1)

4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyloil, R_(f) value: 0.90 (Silica gel: methylene chloride/ethanol=9:1)

EXAMPLE 2 Tert.butyl 4'- (2-n-butyl-5- and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

a) 2-n-butyl-6-nitro-benzimidazole

11.5 g (0.075 mol) of 4-nitro-o-phenylenediamine are introduced inportions at ambient temperature into a mixture of 8.66 g (0.085 mol) ofvaleric acid and 120 ml of phosphorus oxychloride. The mixture is thenheated for 3 hours under reflux. The reaction mixture is separated in1.5 kg of iced water, rendered alkaline using concentrated ammonia andextracted three times using 500 ml of ethyl acetate. The organic phaseis separated off, dried using magnesium sulphate and rotary evaporated.The oily residue is purified over a silica gel column (grain size:0.063-0.2 mm, eluting agent: methylene chloride/0-2% ethanol). Thehomogeneous fractions are evaporated to dryness.

Yield: 10.2 g (62.2% of theoretical),

Melting point: 139°-141° C.

Calculated: C 60.27 H 5.98 N 19.17 Found: 60.30 6.00 19.42

b) 9.5 g (43 mmol) of 2-n-butyl-6-nitro-benzimidazole are dissolved in100 ml of dimethylsulphoxide and treated with 5.3 g (47.6 mmol) ofpotassium tert.butoxide. The mixture is stirred for 30 minutes and 16.6g (47.6 mmol) of tert.butyl 4'-bromomethyl-biphenyl-2-carboxylate areadded. After 2 hours, about 600 ml of water are added to the reactionmixture and it is extracted 3 times using about 200 ml of ethyl acetate.The organic phase is dried using magnesium sulphate and rotaryevaporated. The crude product thus obtained is purified over a silicagel column (grain size: 0.063-0.2 mm, eluting agent: methylenechloride/0-1% ethanol). The homogeneous fractions are evaporated todryness.

Yield: 19.9 g (95.2% of theoretical),

Oil, R_(f) value: 0.50 (Silica gel: methylene chloride+5% ethanol)

Calculated: C 71.73 H 6.43 N 8.65 Found: 72.00 6.66 8.80

The following compounds are obtained in analogous manner:

tert.butyl 4'- (2-n-butyl-4- and7-nitro-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.45 and 0.47 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'- (2-n-butyl-5- and6-methoxy-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.55 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'- (2-n-butyl-5- and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.60 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'- (2-n-butyl-5- and6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.55 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'- (2-n-butyl-5- and6-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil, R_(f)value: 0.20 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'- (2-n-butyl-5- and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.80 (Silica gel: ethyl acetate/ethanol/ammonia=90:10:1)

EXAMPLE 3 Tert.butyl 4'- (5- and6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

18.3 g (37.7 mmol) of tert.butyl 4'- (5- and6-nitro-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate aredissolved in 200 ml of ethanol, 10 g of Raney nickel are added, and themixture is hydrogenated for 3 hours at 50° C. and 5 bar hydrogenpressure. When the uptake of hydrogen is completed, the catalyst isfiltered off under suction and the filtrate is rotary evaporated.

Yield: 17.1 g (100% of theoretical),

Oil, R_(f) value: 0.1 and 0.2 (Silica gel: methylenechloride/ethanol=95:5)

The following compound is prepared in analogous manner:

tert.butyl 4'- (4- and7-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.20 and 0.22 (Silica gel: methylene chloride/ethanol=50:1)

EXAMPLE 4 Tert.butyl 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate (I)and tert.butyl 4'-(5-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate (II)

The isomer mixture of I and II (17.1 g) obtained in Example 3 isseparated over a chromatography column filled with 1,700 ml of silicagel (grain size: 0.063-0.2 mm), I being initially removed by elutionusing methylene chloride/ethanol=98:2.

Yield: 7.32 g (42.8% of theoretical),

Oil, R_(f) value: 0.2 (Silica gel: methylene chloride/ethanol=95:5)

II is then eluted using methylene chloride/ethanol=96:4.

Yield: 9.28 g (54.3% of theoretical),

Oil, R_(f) value: 0.1 (Silica gel: methylene chloride/ethanol=95:5)

The following pure compounds were isolated from the corresponding isomermixtures in analogous manner:

tert.butyl 4'-(4-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Yield: 86.1% of theoretical,

Oil, R_(f) value: 0.25 (Silica gel: methylene chloride/ethanol=99:1)

and

tert.butyl 4'-(7-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Yield: 5.0% of theoretical,

Oil, R_(f) value: 0.30 (Silica gel: methylene chloride/ethanol=99:1)

tert.butyl 4'-(7-benzyloxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Yield: 90.5% of theoretical,

Melting point: 100°-102° C.

and

tert.butyl 4'-(4-benzyloxy-2-n-butyl-7-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Yield: 1.9% of theoretical,

Oil, R_(f) value: 0.20 (Aluminum oxide: cyclohexane/ethyl acetate=4:1)

EXAMPLE 5 Tert.butyl 4'-(2-n-butyl-6-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

a) 2-Pentanoylamido-5-methyl-nitro-benzene

6 g (0.04 mol) of 2-nitro-6-methyl-aniline are dissolved in 50 ml ofpyridine, cooled to 0° C. and treated with 5.3 g (0.04 mol+10%) ofvaleryl chloride while stirring. After stirring for 1 hour at ambienttemperature, the mixture is poured into iced water and the crystals arefiltered off under suction and dried.

Yield: 9 g (96.7% of theoretical),

Melting point: 69°-71° C.

Calculated: C 61.00 H 6.83 N 11.86 Found: 61.21 6.79 11.72

b) 2-Pentanoylamido-5-methyl-aniline

8.5 g (0.035 mol) of 2-pentanoylamino-5-methyl-nitrobenzene aredissolved in 100 ml of methyl alcohol and hydrogenated at ambienttemperature and 5 bar using 2 g of 10% palladium/carbon. When thereaction is completed, the catalyst is filtered off under suction andevaporated in vacuum.

Yield: 7.1 g (94.7% of theoretical),

Melting point: 132°-134° C. (methanol)

Calculated: C 69.87 N 8.80 N 13.58 Found: 69.28 8.74 13.31

c)N-(2-Pentanoylamino-5-methyl-phenyl)-2-tert.butoxycarbonyl-biphenyl-4'-yl-methylamine

2.1 g (0.01 mol) of 2-pentanoylamino-5-methyl-aniline are dissolved in10 ml of dimethylformamide and 5 ml of N,N-diisopropylethylamine,treated with 3.5 g (0.01 mol) of tert.butyl4'-bromomethyl-biphenyl-2-carboxylate and heated at 120° C. withstirring. The reaction is complete after 2 hours and the solvent isdistilled off in vacuum. The oily residue obtained is dissolved in ethylacetate, washed with water and evaporated in vacuum after drying oversodium sulphate. A yellowish oil is obtained after column chromatographyover silica gel (grain size: 0.06-0.2 mm, eluting agent: methylenechloride).

Yield: 3.8 g (80.0% theoretical),

Oil, R_(f) value: 0.75 (Silica gel: methylethylketone/xylene=1:1)

Calculated: C 76.24 H 7.68 N 5.93 Found: 76.16 7.85 5.87

d) Tert.butyl 4'-(2-n-butyl-6-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

3.6 g (0.076 mol) ofN-(2-pentanoylamino-5-methylphenyl)-2-tert.butoxycarbonyl-biphenyl-4'-yl-methylamineare taken up in 5 ml of diglyme and heated to reflux. The reaction iscompleted after 2 hours, the reaction product is dissolved in ethylacetate, washed with water and evaporated in vacuum after drying oversodium sulphate. A yellowish oil is obtained after column chromatographyover silica gel (grain size: 0.06-0.2 mm, eluting agent: methylenechloride+1% ethanol).

Yield: 2.1 g (61.7% of theoretical),

Oil, R_(f) value: 0.6 (Silica gel: methylethylketone/xylene=1:2)

Calculated: C 79.26 H 7.54 N 6.16 Found: 79.12 7.46 6.09

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-n-butyl-6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.6 (Silica gel: methylethylketone/xylene=1:2)

tert.butyl 4'-(2-n-butyl-6-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.65 (Silica gel: methylethylketone/xylene=1:2)

EXAMPLE 6 Tert.butyl 4'-(2-n-butyl-5-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

a) 2-Pentanoylamino-5-methoxy-nitrobenzene

4.2 g (0.025 mol) of 2-nitro-4-methoxy-aniline are dissolved in 30 ml ofpyridine, cooled to 0° C. and treated with 3.3 g (0.0275 mol) of valerylchloride with stirring. After stirring for 1 hour at ambienttemperature, the mixture is poured into iced water, the crystals arefiltered off under suction and dried.

Yield: 6 g (95.2% of theoretical),

Melting point: 74°-75° C.

C₁₉ N₁₀ N₈ O₆ (252.27)

Calculated: C 57.13 H 6.39 N 11.11 Found: 57.43 6.45 10.97

b)N-(2-Nitro-4-methoxy-phenyl)-N-pentanoyl-(2-tert.butoxycarbonyl-biphenyl-4'-yl)-methylamine

2.5 g (0.01 mol) of 2-pentanoylamino-5-methoxy-nitrobenzene aredissolved in 30 ml of dimethylformamide, treated with 550 mg (0.11 mol)of sodium hydride (50% in oil) and stirred for 30 minutes at 80° C. 3.5g (0.01 mol) of tert.butyl 4'-bromomethyl-biphenyl-2-carboxylate arethen added and stirred for a further 2 hours at 80° C. The solvent isdistilled off in vacuum, the oily residue obtained is dissolved in ethylacetate, washed with water and evaporated in vacuum after drying oversodium sulphate. A yellowish oil is obtained after column chromatography(silica gel: 0.06-0.2 mm, eluting agent: methylene chloride).

Yield: 4.0 g (78.4% of theoretical),

Oil, R_(f) value: 0.8 (Silica gel: methylethylketone/xylene=1:2)

C₃₀ H₃₄ N₂ O₆ (518.61)

Calculated: C 69.48 H 6.61 N 5.40 Found: 69.31 6.53 5.39

c)N-(2-Amino-4-methoxy-phenyl)-N-pentanoyl-(2-tert.butoxycarbonyl-biphenyl-4'-yl)-methylamine

3.8 g (0.007 mol) ofN-(2-nitro-4-methoxy-phenyl)-N-pentanoyl-(2-tert.butoxycarbonyl-biphenyl-4'-yl)-methylamineare dissolved in 100 ml of methanol and hydrogenated at ambienttemperature and 5 bar in the presence of 1 g of 70% palladium/carbon.After the reaction is completed, the catalyst is filtered off undersuction and evaporated in vacuum.

Yield: 3.2 g (93.6% of theoretical),

Oil, R_(f) value: 0.5 (Silica gel: methylethylketone/xylene=1:2)

C₃₀ H₃₆ N₂ O₄ (488.63)

Calculated: C 73.74 H 7.43 N 5.73 Found: 73.59 7.40 5.72

d) Tert.butyl 4'-(2-n-butyl-5-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

3 g (0.006 mol) ofN-(2-amino-4-methoxy-phenyl)-N-pentanoyl-(2-tert.butoxycarbonyl-biphenyl-4'-yl)-methylamineare dissolved in 100 ml of glacial acetic acid and heated to reflux withstirring. After one hour the solvent is distilled off and the resultingoil is chromatographed for further purification over silica gel (grainsize: 0.06-0.2 mm, eluting agent: methylene chloride/ethanol=19:1).

Yield: 2.3 g (82.1% of theoretical),

Oil, R_(f) value: 0.7 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

C₃₀ H₃₄ N₂ O₃ (470.61)

Calculated: C 76.56 H 7.28 N 5.95 Found: 76.36 7.31 5.79

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-n-butyl-5-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.7 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(5-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.5 (Silica gel: ethyl acetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-5-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.8 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-7-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.49 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-5,7-difluoro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.27 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'-(2-n-butyl-5-acetyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.30 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'-(2-n-butyl-6-dimethylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(7-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.30 (Aluminium oxide: methylene chloride/ethanol=99:1)

tert.butyl 4'-(6-N-benzyl-methylamino)-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-5-dimethylamino-sulphonyl-3-N-oxido-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate(prepared by incomplete reduction of the nitro group and subsequentcyclisation) melting point: 59°-62° C.

tert.butyl 4'-(7-benzyloxy-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(4-benzyloxy-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.65 (Silica gel: methylethylketone/xylene=1:4)

tert.butyl 4'-(2-n-butyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.80 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-4-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylethylketone/xylene=1:2)

tert.butyl 4'-(2,5-di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2,6-di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(6-benzyloxy-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Silica gel: methylethylketone/xylene=1:2)

tert.butyl 4'-(2-n-butyl-6-methylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.10 (Silica gel: methylene chloride/ethanol=50:1)

tert.butyl 4'-(2-n-butyl-6-cyclohexylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Silica gel: ethyl acetate/petroleum ether=60:40)

tert.butyl 4'-(2-n-butyl-6-(3-cyclohexyl-piperidino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.65 (Silica gel: methylene chloride/ethanol=9:1)

tert.butyl 4'-(2-n-butyl-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 182°-184° C.

tert.butyl 4'-(2-n-butyl-6-(n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2,5-di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.30 (Silica gel: methylethylketone/xylene=1:4)

tert.butyl 4'-(2,6-di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate oil,R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1:4)

EXAMPLE 7 tert.butyl 4'-(2-n-butyl-5-(n-butylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

2.09 g (4.4 mmol) of tert.butyl 4'-(5-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate aredissolved in 50 ml of tetrahydrofuran and treated with 2.0 ml oftriethylamine and 2.0 ml of n-butylisocyanate. The reaction mixture isheated at reflux for 4 hours, rotary evaporated, and the residue ispurified over a silica gel column (grain size: 0.063 mm-0.2 mm, elutingagent: methylene chloride/0-2% ethanol). The homogeneous fractions areevaporated to dryness.

Yield: 2.1 g (86.4% of theoretical),

Oil, R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=19:1).

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-n-butyl-6-phenylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateamorphous substance, R_(f) value: 0.30 (Silica gel: methylenechloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateamorphous substance, R_(f) value: 0.25 (Silica gel: methylenechloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-4-ethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateamorphous substance, R_(f) value: 0.50 (Silica gel: methylenechloride/ethanol=19:1)

tert.butyl 4'-(6-aminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 210°-211° C.

tert.butyl 4'-(2-n-butyl-6-(n-hexylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 142°-143° C.

tert.butyl 4'-(2-n-butyl-4-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 104°-106° C. (amorphous)

tert.butyl 4'-(2-n-butyl-5-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 118°-120° C. (amorphous)

ethyl 4'-(2-n-butyl-7-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 152°-154° C.

tert.butyl 4'-(6-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 175°-176° C.

tert.butyl 4'-(2-n-butyl-6-cyclohexylaminothiocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 91°-93° C. (amorphous)

tert.butyl 4'-(5-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 196°-197° C.

tert.butyl 4'-(2-n-butyl-6-benzylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 163°-165° C.

tert.butyl 4'-(6-allylaminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.10 (Silica gel: methylene chloride/ethanol=19:1)

ethyl 4'-(2-n-butyl-6-(tetrahydropyran-2-yl-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 86°-88° C. (amorphous)

tert.butyl 4'-(2-n-butyl-6-(tetrahydropyran-2-yl-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.30 (Silica gel: methylethylketone/xylene=5:2)

4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-phthalimino-biphenyloil, R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=9:1)

4'-(6-adamant-1-yl-aminocarbonylamino)-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-3-carboxylicacid melting point: 251°-253° C.

tert.butyl 4'-(6-(adamant-1-yl-aminocarbonylamino)-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 196°-198° C.

tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonylmethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.30 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-n-butyl-5-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: methylethylketone/xylene=1:2)

tert.butyl 4'-(6-(n-butylaminocarbonylamino)-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.7 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.7 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: methylethylketone=5:2)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.8 (Silica gel: methylethylketone=5:2)

tert.butyl 4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Aluminium oxideplate:ethyl acetate/petroleumether=3:7)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Aluminium oxide: ethyl acetate/petroleumether=4:1)

tert.butyl 4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (Silica gel: ethyl acetate/petroleum ether=4:1)

tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Aluminium oxide: ethyl acetate/petroleumether=7:3)

tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Aluminium oxide: ethyl acetate/petroleumether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Aluminium oxide: ethyl acetate/petroleumether=4:6)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 106°-108° C. (amorphous)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-(2-trifluoromethylphenyl-aminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylateoil, R_(f) value: 0.90 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-propylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-ethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Silica gel: ethyl acetate/petroleum ether=7:3)

tert.butyl 4'-(2-(1-trans-butenyl)-6-cyclohexylamino-carbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Aluminium oxide: methylenechloride/ethanol=50:1)

tert.butyl 4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-(1H-triphenyl-methyl-tetrazol-5-yl)-biphenylmelting point: 183°-187° C.

4'-(2-n-butyl-6-(N-cyclohexylaminocarbonylmethylamino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenylmelting point: 185°-186° C.

tert.butyl 4'-(2-n-butyl-6-cyclohexylaminocarbonyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 76°-78° C. (amorphous)

tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-N-(3-cyclohexyl-n-propyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.15 (aluminium oxide: petroleum ether/ethylacetate=2:3)

4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-1-cyano-2-phenyl-naphthalene

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-2-phenyl-napthalene-1-carboxylate

4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyl

tert.butyl 4'-(2-n-butyl-6-(N-(n-dodecylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (aluminium oxide: petroleum ether/ethylacetate=3:7)

tert.butyl 4'-(2-n-butyl-6-(N-(cyclohexylaminocarbonyl)-n-octylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (aluminium oxide: petroleum ether/ethylacetate=3:2)

tert.butyl 4'-(2-n-butyl-6-(N-(n-dodecylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (aluminium oxide: petroleum ether/ethylacetate=2:3)

EXAMPLE 8 Tert.butyl 4'-(2-n-butyl-4-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

1.6 g (3.5 mmol) of tert.butyl 4'-(4-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate aredissolved in 30 ml of pyridine and 0.52 ml (5.0 mmol) of butyrylchloride is added dropwise at ambient temperature with stirring. Afterone hour the solvent is distilled off and the residue is mixed withabout 20 ml of diethylether. The precipitate is filtered off undersuction and dried at 50° C. in vacuum.

Yield: 1.75 g (94.6% of theoretical),

Melting point: 167°-168° C.

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-n-butyl-5-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylene chloride/ethanol=9:1)

tert.butyl 4'-(2-n-butyl-5-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.80 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-5-methanesulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.75 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-6-isopropylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateamorphous substance, R_(f) value: 0.55 (Silica gel: methylenechloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-6-ethoxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateamorphous substance, R_(f) value: 0.30 (Silica gel: methylenechloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-5-(tert.butoxycarbonylaminoacetamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 101°-103° C. (amorphous)

tert.butyl 4'-(2-n-butyl-6-(N-butanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylene chloride/ethanol=19:1)

ethyl 4'-(2-n-butyl-7-butanesulphonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=19:1)

ethyl 4'-(2-n-butyl-5-propanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 221°-223° C.

tert.butyl 4'-(6-acetamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 192°-194° C.

tert.butyl 4'-(2-n-butyl-6-propanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 133°-135° C.

tert.butyl 4'-(6-butanoylamino-2-n-butyl-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 127°-129° C.

tert.butyl 4'-(2-n-butyl-6-n-pentanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.6 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-6-dimethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.4 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: methylene chloride/ethanol=19:1)

tert.butyl 4'-(2-n-butyl-6-phenylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateR_(f) value: 0.30 (Silica gel: methylene chloride/ethanol=50:1) meltingpoint: 178°-180° C.

tert.butyl 4'-(2-n-butyl-6-cyclohexylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateR_(f) value: 0.30 (Silica gel: ethyl acetate/petroleum ether=4:1)melting point: 64°-66° C. (amorphous)

tert.butyl 4'-(2-n-butyl-6-cyclohexylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateR_(f) value: 0.70 (Silica gel: ethyl acetate/petroleum ether=9:1)melting point: 72°-76° C. (amorphous)

tert.butyl 4'-(6-benzyloxycarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateR_(f) value: 0.80 (Silica gel: ethyl acetate/petroleum ether=9:1)melting point: 84°-86° C.

tert.butyl 4'-(2-n-butyl-6-cyclohexylmethylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: petroleum ether/ethylacetate/ethanol=2.5:2.5:0.5)

tert.butyl 4'-(2-n-butyl-6-cyclohexylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.50 (Silica gel: petroleum ether/ethylacetate/ethanol=2.5:2.5:0.5)

tert.butyl 4'-(2-n-butyl-6-(N-methyl-n-butyl-aminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Silica gel: petroleum ether/ethylacetate/ethanol=6:3:1+1% glacial acetic acid)

tert.butyl 4'-(2-n-butyl-5-(n-butylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.75 (Silica gel: petroleum ether/ethyl acetate=1:2+1%glacial acetic acid)

tert.butyl 4'-(2-n-butyl-6-(2-isopropyl-5-methyl-cyclohexyloxycarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: ethyl acetate/petroleum ether=60:40)

tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.65 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-cyclohexylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 65°-66° C. (amorphous)

tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: ethyl acetate/petroleum ether=7:3)

tert.butyl 4'-(2-n-butyl-6-(n-hexyloxycarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'- (2-n-butyl-6-(5,7-dioxo-1H,3H-imidazo1,5-c!thiazol-6-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Aluminium oxide: ethyl acetate/petroleumether=7:3)

tert.butyl 4'-(2-n-butyl-6-(N-(n-butanoyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-(4-methoxycarbonyl-thiazolidin-3-ylcarbonyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylcarbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.55 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylcarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-(n-butanoyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-6-isopropylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.15 (Silica gel: ethyl acetate/petroleum ether=7:3)

tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (Silica gel: ethyl acetate/petroleum ether=6:4)

tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.70 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: ethyl acetate/petroleum ether=4:1)

tert.butyl 4'-(2-n-butyl-6-diethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.20 (Silica gel: ethyl acetate/petroleum ether=9:1)

tert.butyl 4'-(2-n-butyl-6-(dimethylaminoacetamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.40 (Silica gel: methylethylketone/xylene=5:2)

tert.butyl 4'-(2-n-butyl-6-(2,2-dimethylpropionylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.60 (Silica gel: ethyl acetate/petroleum ether=9:1)

tert.butyl 4'-(2-n-butyl-6-cyclopentylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.35 (Silica gel: ethyl acetate/petroleum ether=7:3)

tert.butyl 4'-(2-n-butyl-6-cyclopropylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 175°-177° C.

tert.butyl 4'-(2-n-butyl-6-cyclohexyloxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 68°-70° C. (amorphous)

4'-(2-n-butyl-6-dimethylaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyloil, R_(f) value: 0.75 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-6-morpholinocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatemelting point: 74°-76° C.

tert.butyl 4'-(2-n-butyl-6-pyrrolidinocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

EXAMPLE 9 4'- (2-Hydroxybenzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

0.9 g (2.25 mmol) of tert.butyl 4'-(2-hydroxybenzimidazol-1-yl)-methyl!biphenyl-2-carboxylate are dissolvedin 10 ml of methylene chloride and treated with 10 ml of trifluoroaceticacid. The solution is stirred for 2 hours at ambient temperature andthen evaporated to dryness on a rotary evaporator. The oily residue isdissolved in 50 ml of methylene chloride and extracted by shaking twiceusing water. The organic phase is dried using magnesium sulphate andevaporated to dryness. The crystalline residue thus obtained is mixedwith a small amount of diethylether, filtered under suction and dried invacuum at 50° C.

Yield: 0.75 g (97.4% of theoretical),

Melting point: 303°-304° C.

C₂₁ H₁₆ N₂ O₃ (344.37)

Calculated: C 73.24 H 4.68 N 8.13 Found: 73.07 4.81 7.95

The following compounds are obtained in analogous manner:

4'- (2,5-di-n-butylbenzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidM.p.: 199°-201° C.

4'- (2,6-di-n-butylbenzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidM.p.: 188°-190° C.

EXAMPLE 10 4'-(2-n-Butyl-6-methoxybenzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-methoxybenzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 73.9% of theoretical,

Oil, R_(f) value: 0.6 (Silica gel: ethylacetate/ethanol/ammonia=50:45:5)

C₂₈ H₂₆ N₂ O₃ (414.51)

Calculated: C 75.34 H 6.23 N 6.76 Found: 75.27 6.03 6.52

EXAMPLE 11 4'-(2-n-Butyl-4-methyl-7-(2-diethylamino-ethoxy)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid dihydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-methyl-7-(2-diethylamino-ethoxy)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 94.2% of theoretical,

Melting point: 94°-96° C.

C₂₃ H₃₃ N₃ O₃ ×2 H₂ O (549.72)

Calculated: C 69.92 H 7.88 N 7.64 Found: 69.62 7.60 7.40

Example 12 4'-(2-Ethylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-ethylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 92.9% of theoretical,

Melting point: 197°-198° C.

C₂₃ H₃₀ N₂ O₂ S (388.48), Calculated: C, 71.11; H, 5.19; N, 7.21; S,8.25. Found: C, 71.12; H, 5.13; N, 7.23; S, 8.31.

Example 13 4'-(2-n-Propylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-propylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 96.8% of theoretical,

Melting point: 139°-141° C.

C₂₅ H₂₄ N₂ O₂ S (416.54), Calculated: C, 72.09; H, 5.81; N, 6.73; S,7.70. Found: C, 71.82; H, 5.83; N, 6.57; S, 7.43.

Example 14 4'- (2-Methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid×0.33 HCl

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 93.2% of theoretical,

Melting point: 255°-256° C.

C₂₂ H₁₈ N₂ O₂ ×0.33 HCl (354.54), Calculated: C, 74.53; H, 5.21; N,7.90; Cl, 3.32. Found: C, 74.60; H, 5.14; N, 8.16; Cl, 3.49.

Example 15 4'-(2-Methylmercapto-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methylmercapto-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 88.2% of theoretical,

Melting point: 197°-199° C.

C₂₂ H₁₀ N₂ O₂ S (374.46), Calculated: C, 70.57; H, 4.84; N, 7.48; S,8.56. Found: C, 70.30; H, 4.87; N, 7.25; S, 8.25.

Example 16 4'- (2-Methyl-5- and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methyl-5- and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 71.1% of theoretical,

Melting point: 285°-288° C.

C₂₃ H₁₇ N₃ O₄ (387.39), Calculated: C, 68.21; H, 4.42; N, 10.85. Found:C, 67.96; H, 4.40; N, 10.83.

Example 17 4'- (2-Methyl-5-and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methyl-5- and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 79.5% of theoretical,

Melting point: 261°-262° C.

C₂₆ H₂₅ N₃ O₃ (427.50), Calculated: C, 73.05; H, 5.89; N, 9.83. Found:C, 72.85; H, 5.90; N, 9.80.

Example 18 4'-(2-(2-Methylpropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methylpropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 71.9% of theoretical,

Melting point: 211°-212° C.

C₂₅ H₂₄ N₂ O₂ (384.48), Calculated: C, 78.10; H, 6.29; N, 7.29. Found:C, 77.95; H, 6.22; N, 7.15.

Example 19 4'-(2-Methoxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methoxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 80.3% of theoretical,

Melting point: 195°-197° C.

C₂₃ H₂₀ N₂ O₃ (372.43), Calculated: C, 74.18; H, 5.41; N, 7.52. Found:C, 73.99; H, 5.39; N, 7.43.

Example 20 4'-(2-Pyridyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-pyridyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 50.0% of theoretical,

Melting point: 262°-264° C.

C₂₀ H₁₈ N₃ O₃ (405.45), Calculated: C, 77.02; H, 4.72; N, 10.36. Found:C, 77.21; H, 4.58; N, 10.20.

Example 21 4'- (5- and6-Methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'- (5- and6-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 92.0% of theoretical,

Melting point: 228°-230° C.

C₂₃ H₁₈ N₂ O₂ (342.396), Calculated: C, 77.17; H, 5.30; N, 8.18. Found:C, 76.94; H, 5.23; N, 7.93.

Example 22 4'- (2-Phenyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-phenyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 56.8% of theoretical,

Melting point: 275°-277° C.

C₂₇ H₂₀ N₂ O₂ (404.47), Calculated: C, 80.18; H, 4.98; N, 6.93. Found:C, 79.90; H, 5.05; N, 6.92.

Example 23 4'-(2-Thiazol-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(thiazol-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 94.6% of theoretical,

Melting point: 284°-286° C.

C₂₄ H₁₇ N₃ O₂ S (411.48), Calculated: C, 70.06; H, 4.16; N, 10.21; S,7.79. Found: C, 69.90; H, 4.29; N, 9.97; S, 7.59.

Example 24 4'-(2-(3,5-Dimethyl-pyrazol-1-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(3,5-dimethyl-pyrazol-1-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 87.2% of theoretical,

Melting point: 185°-187° C.

C₂₆ H₂₂ N₄ O₂ (422.49), Calculated: C, 73.92; H, 5.25; N, 13.26. Found:C, 73.86; H, 5.37; N, 13.27.

Example 25 4'-(Fur-2-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(fur-2-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 78.4% of theoretical,

Melting point: 263°-265° C.

C₂₅ H₁₈ N₂ O₃ (394.43), Calculated: C, 76.13; H, 4.60; N, 7.10. Found:C, 75.94; H, 4.64; N, 6.83.

Example 26 4'-(2-Aminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-aminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 53.3% of theoretical,

Melting point: 214°-216° C.

C₂₂ H₁₈ N₄ O₃ ×H₂ O (404.42), Calculated: C, 65.34; H, 4.98; N, 13.85.Found: C, 65.18; H, 5.05; N, 13.61.

Example 27 4'-(2-Isopropyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-isopropyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 80% of theoretical,

Melting point: 206°-208° C.

C₂₄ H₂₂ N₂ O₂ (370.46), Calculated: C, 77.81; H, 5.99; N, 7.56. Found:C, 77.55; H, 5.97; N, 7.43.

Example 28 4'-(7-Benzyloxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(7-benzyloxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 85.5% of theoretical,

Melting point: 217°-219° C.

C₂₃ H₂₂ N₂ O₃ ×CF₃ COOH (618.66), Calculated: C, 67.95; H, 5.37; N,4.52. Found: C, 68.19; H, 5.56; N, 4.74.

Example 29 4'-(2-Hydroxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-hydroxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 81.9% of theoretical,

Melting point: 188°-190° C.

C₂₂ H₁₈ N₂ O₃ ×CF₃ COOH (472.42), Calculated: C, 61.02; H, 4.05; N,5.93. Found: C, 61.23; H, 4.08; N, 5.91.

Example 30 4'-(2-(3-Hydroxypropyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(3-hydroxypropyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 58.8% of theoretical,

Melting point: 150°-152° C.

C₂₄ H₂₂ N₂ O₃ ×CH₃ COOH (500.47), Calculated: C, 62.40; H, 4.63; N,5.60. Found: C, 62.13; H, 4.70; N, 5.83.

Example 31 4'- (2-Methyl-5- and6-(N-(2-methoxyacetyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methyl-5- and6-(N-(2-methoxyacetyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 84.8% of theoretical,

Melting point: 186°-188° C.

C₂₀ H₃₁ N₃ O₆ (485.58), Calculated: C, 71.73; H, 6.43; N, 8.65. Found:C, 72.67; H, 6.68; N, 8.74.

Example 32 4'-(2-(1-Methylpropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(1-methylpropyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 80% of theoretical,

Melting point: 147°-148° C.

C₂₅ H₂₄ N₂ O₂ (384.48), Calculated: C, 78.10; H, 6.29; N, 7.29. Found:C, 77.91; H, 6.23; N, 7.37.

Example 33 4'-(2-Methylbutyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(2-methylbutyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 60% of theoretical,

Melting point: 209°-210° C.

C₂₆ H₂₈ N₂ O₂ (398.51), Calculated: C, 78.36; H, 6.58; N, 7.03. Found:C, 78.27; H, 6.51; N, 6.99.

Example 34 4'- (2-Methyl-4- and6-(N-(2-methoxyethyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methyl-5- and6-(N-(2-methoxyethyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 46.5% of theoretical,

Melting point: 102°-106° C.

C₂₅ H₃₃ N₃ O₃ (471.598), Calculated: C, 73.86; H, 7.05; N, 8.91. Found:C, 73.60; H, 7.13; N, 8.85.

Example 35 4'-(2-n-Pentyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-pentyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 87% of theoretical,

Melting point: 181°-183° C.

C₂₅ H₂₆ N₂ O₂ (387.51), Calculated: C, 78.36; H, 6.58; N, 7.03. Found:C, 78.12; H, 6.42; N, 7.09.

Example 36 4'- (Benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate and trifluoroaceticacid.

Yield: 90.9% of theoretical,

Melting point: 217°-219° C.

C₃₁ H₁₈ N₂ O₂ (328.37), Calculated: C, 76.81; H, 4.91; N, 8.53. Found:C, 77.03; H, 5.00; N, 8.42.

Example 37 4'-(2-n-Butyl-4-methyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-methyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 86.6% of theoretical,

Melting point: 216°-218° C.

C₂₇ H₂₆ N₂ O₃ (428.54), Calculated: C, 75.68; H, 6.59; N, 6.54. Found:C, 75.48; H, 6.59; N, 6.45.

Example 38 4'-(2-n-Propyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-propyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 85.2% of theoretical,

Melting point: 237°-238° C.

C₂₄ H₂₃ N₂ O₂ (370.45), Calculated: C, 77.81; H, 5.99; N, 7.56. Found:C, 78.08; H, 5.74; N, 7.37.

Example 39 4'- (2-Ethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-ethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 81.6% of theoretical,

Melting point: 251°-253° C.

C₂₃ H₂₀ N₂ O₂ (356.42), Calculated: C, 77.51; H, 5.66; N, 7.86. Found:C, 77.72; H, 5.64; N, 7.59.

Example 40 4'-(2-Ethylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidsemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-ethylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 96.1% of theoretical,

Melting point: 139°-141° C.

C₂₄ H₂₂ N₂ O₂ S×1/2CF₃ COOH (459.52), Calculated: C, 65.35; H, 4.94; N,6.10; S, 6.98. Found: C, 65.24; H, 5.00; N, 6.18; S, 6.98.

Example 41 4'-(2-Methylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidsemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-methylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 98.6% of theoretical,

Melting point: 147°-149° C.

C₂₃ H₂₀ N₂ O₂ S×1/2CF₃ COOH (445.495), Calculated: C, 64.71; H, 4.64; N,6.29; S, 7.30. Found: C, 64.70; H, 5.04; N, 6.51; S, 6.91.

Example 42 4'- (2-Chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 84.0% of theoretical,

Melting point: 169°-171° C.

C₂₁ H₁₅ ClN₂ O₂ (362.815), Calculated: C, 69.52; H, 4.17; N, 7.72; Cl,9.77. Found: C, 69.39; H, 4.13; N, 7.66; Cl, 9.72.

Example 43 4'-(2-n-Butylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 88.0% of theoretical,

Melting point: 160°-162° C.

C₂₃ H₂₄ N₂ O₂ S (416.54), Calculated: C, 72.09; H, 5.81; N, 6.73; S,7.70. Found: C, 71.93; H, 5.75; N, 6.74; S, 7.71.

Example 44 4'-(2-n-Butyl-5-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacidhydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 71.3% of theoretical,

Melting point: 187°-189° C.

C₂₇ H₂₇ N₃ O₃ ×H₂ O (459.54), Calculated: C, 70.56; H, 6.36; N, 9.14.Found: C, 70.40; H, 6.22; N, 9.08.

Example 45 4'-(2-(4-Methoxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(4-methoxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 87.5% of theoretical,

Melting point: 283°-286° C.

C₂₈ H₂₃ N₂ O₃ (434.50), Calculated: C, 77.40; H, 5.10; N, 6.45. Found:C, 77.45; H, 5.20; N, 6.44.

Example 46 4'-(2-n-Propylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-propylthio-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 90.5% of theoretical,

Melting point: 219°-220° C.

C₂₄ H₂₂ N₂ O₂ S (402.51), Calculated: C, 71.62; H, 5.51; N, 6.96; S,7.97. Found: C, 71.47; H, 5.51; N, 6.75; S, 8.09.

Example 47 4'-(2-n-Butylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidsemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 80.0% of theoretical,

Melting point: 247°-249° C.

C₂₃ H₂₃ N₃ O₂ ×1/2CF₃ COOH (456.50), Calculated: C, 68.41; H, 5.63; N,9.20. Found: C, 68.56; H, 5.84; N, 9.07.

Example 48 4'- (2-(4-Methoxyphenyl)-5- and6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(4-methoxyphenyl)-5- and6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 76.3% of theoretical,

Melting point: 234°-236° C.

C₂₀ H₂₁ ClN₂ O₃ (468.95), Calculated: C, 71.71; H, 4.51; N, 5.97; Cl,7.56. Found: C, 71.57; H, 4.39; N, 5.85; Cl, 7.79.

Example 49 4'-(2-n-Butyl-5-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 66.2% of theoretical,

Melting point: 203°-205° C.

C₂₆ H₂₆ N₂ O₃ (414.51), Calculated: C, 75.34; H, 6.323; N, 6.76. Found:C, 75.19; H, 6.31; N, 6.61.

Example 50 4'- (2-n-Butyl-5- and6-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5- and6-acetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 83.7% of theoretical,

Melting point: 117°-119° C.

C₂₇ H₂₇ N₃ O₃ (441.54), Calculated: C, 73.45; H, 6.16; N, 9.52. Found:C, 73.25; H, 6.23; N, 9.47.

Example 51 4'- (2-n-Butyl-5- and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5- and6-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 80.0% of theoretical,

Melting point: 123°-127° C.

C₂₉ H₃₁ N₃ O₃ (469.59), Calculated: C, 74.18; H, 6.65; N, 8.95. Found:C, 73.96; H, 6.19; N, 8.99.

Example 52 4'-(6-(N-Benzyl-methylamino)-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-(N-benzyl-methylamino)-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 82.0% of theoretical,

Melting point: 237°-238° C.

C₂₃ H₃₃ N₃ O₂ (503.64), Calculated: C, 78.70; H, 6.60; N, 8.34. Found:C, 78.68; H, 6.71; N, 8.44.

Example 53 4'-(2-n-Butyl-5-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 70.6% of theoretical,

Melting point: 191°-193° C.

C₂₃ H₂₃ ClN₂ O₂ (418.92), Calculated: C, 71.68; H, 5.53; N, 6.69; Cl,8.46. Found: C, 71.48; H, 5.40; N, 6.53; S, 8.43.

Example 54 4'- (2-n-Butyl-5- and6-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5- and6-methoxy-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 84.1% of theoretical,

Melting point: 128°-133° C.

C₂₃ H₂₃ N₂ O₃ (414.51), Calculated: C, 75.34; H, 6.32; N, 6.76. Found:C, 75.32; H, 6.14; N, 6.75.

Example 55 4'-(2-n-Butyl-7-n-butoxy-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacidtrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-7-n-butoxy-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylatein methylene chloride.

Yield: 63.3% of theoretical,

Melting point: 172°-173° C.

C₂₆ H₂₄ N₂ O₃ ×CF₃ COOH (584.65), Calculated: C, 65.74; H, 6.03; N,4.73.Found: C, 66.52; H, 6.15; N, 4.95.

Example 56 2-n-Butyl-1-(2-carboxy-biphenyl-4'-yl)methyl!-6,7-dihydro-7,7-dimethyl-5-ethyl-5H-pyrrolo2,3-f!benzimidazol-6-one semi-hydrate

5 g (10.3 mmol) of 6-amino-5-(2-tert.butoxycarbonyl-biphenyl-4'-yl)-methyl!-amino-3,4-dimethyl-1-ethyl-indol-2-oneand 5 ml of valeric acid are heated at reflux for 4 hours. Aftercooling, the mixture is stirred into 50 ml of saturated aqueous sodiumcarbonate solution. It is extracted by shaking 3 times using 30 ml ofmethylene chloride each time. The methylene chloride phase is driedusing sodium sulphate and evaporated in vacuum. The crude product ispurified using a silica gel column (eluting agent: ethylacetate/ethanol/ammonia=90:10:1).

Yield: 1.55 g (30.3% of theoretical),

Melting point: 185°-187° C.

C₃₁ H₂₃ N₃ O₃ ×1/2H₂ O (504.64), Calculated: C, 73.81; H, 6.79; N, 8.33,Found: C, 73.91; H, 6.86; N, 7.25; S, 8.36.

Example 57 4'-(2-n-Butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenylhydrate

0.9 g (1.7 mmol) of 4'-(2-n-butyl-7-benzyloxy-4-methyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl,dissolved in 100 ml of methanol, are hydrogenated at ambient temperatureat 5 bar hydrogen pressure in the presence of 0.9 g of 20% palladiumhydroxide on carbon. The catalyst is then filtered off under suction andthe filtrate is evaporated to dryness in vacuum. The crude product isrecrystallised from acetone/ether and dried at 50° C. in vacuum.

Yield: 0.72 g (97.3% of theoretical),

Melting point: 331°-333° C.

C₂₅ H₂₆ N₆ O×H₂ O (456.56), Calculated: C, 68.40; H, 6.18; N, 18.40.Found: C, 68.64; H, 6.18; N, 18.55.

The following compounds are obtained in analogous manner:

4'-2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-trifluoroacetamino-biphenyl

melting point: 243°-245° C.

4'-2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-trifluoromethanesulphonamino-biphenyl

melting point: 160°-162° C.

tert.butyl 4'-2-n-butyl-7-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.60 (silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-2-n-butyl-6-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.55 (silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-2-n-butyl-4-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

melting point: 91°-93° C.

tert.butyl 4'-2-n-butyl-5-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.60 (silica gel: methylethylketone/xylene=1:2)

4'-2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-phthalimino-biphenyl

melting point: 224°-226° C.

Example 58 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl a)4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyltetrazol-5-yl)-biphenyl

0.87 g (5 mmol) of 2-n-butyl-benzimidazole is dissolved in 20 ml ofdimethylsulphoxide and 0.61 g (5.5 mmol) of potassium tert.butoxide isadded with stirring. After 1/2 hour,4'-bromomethyl-2-(1-triphenylmethyl-1H-tetrazol-5-yl)-biphenyl is addedand the mixture is stirred for 3 hours at ambient temperature. It ispoured into about 50 ml of iced water and extracted by shaking 3 timesusing 30 ml of ethyl acetate each time. The ethyl acetate phase isextracted by shaking using 30 ml of water, dried over sodium sulphateand evaporated to dryness. The crude product is purified over a silicagel column (grain size: 0.063-0.2 mm, eluting agent: methylenechloride/ethanol=100:1).

Yield: 2.1 g (64.6% of theoretical),

Melting point: 85°-87° C.

C₄₄ H₃₆ N₆ (650.84), Calculated: C, 81.20; H, 5.88; N, 12.91. Found: C,80.97; H, 5.90; N, 12.66.

b) 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

2 g (3 mmol) of 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenylare dissolved in a mixture of 10 ml of methylene chloride and 10 ml ofmethanol, treated with 10 ml of etherified hydrochloric acid and stirredat ambient temperature for 3 hours. The mixture is rotary evaporated todryness in vacuum. The residue is dissolved in methanol, renderedalkaline using ammonia and rotary evaporated once again. The crudeproduct is purified over a silica gel column (grain size: 0.063-0.2 mm,eluting agent: methylene chloride/ethanol/ammonia=19:1:0.1). The productis crystallised from ether and dried at 50° C. in vacuum.

Yield: 1.02 g (81.6% of theoretical),

Melting point: 241°-243° C.

C₂₅ H₂₄ N₆ (408.52), Calculated: C, 73.50; H, 5.92; N, 20.57. Found: C,73.34; H, 5.92; N, 20.47.

Example 59 4'-(2-n-Butyl-7-benzyloxy-4-methyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenylsemi-hydrate

A mixture of 3.8 g (7.1 mmol) of ammonium chloride, 4.5 g (69 mmol) ofsodium azide, 20 ml of dimethylformamide and 2.2 g (4.53 mmol) of 4'-(2-n-butyl-7-benzyloxy-4-methyl-benzimidazol-1-yl)-methyl!-2-cyano-biphenylis heated at 120° C. internal temperature for 36 hours with stirring.The sodium chloride formed is filtered off and the filtrate is rotaryevaporated in vacuum. 50 ml of water are added to the oily residue andthe solution is adjusted to pH 2 using concentrated hydrochloric acidwith cooling. The oily crude product is filtered off, taken up in 50 mlof methylene chloride and dried over sodium sulphate. It is thenpurified over a silica gel column (grain size 0.063-0.2 mm, elutingagent: methylene chloride/ethanol=19:1). The homogeneous fractions areevaporated to dryness in vacuum and the residue is dried at 50° C.

Yield: 1.6 g (68% of theoretical),

Melting point: 112°-116° C.

C₃₃ H₃₂ N₆ O×1/2H₂ O (537.66), Calculated: C, 73.73; H, 6.18; N, 15.63.Found: C. 73.55; H, 6.33; N, 15.91.

Example 60 4'-(7-Acetoxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

0.55 g (1 mmol) of 4'-(2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate is dissolved in 20 ml of pyridine. 0.5 ml (7 mmol)of acetyl chloride is added dropwise to the mixture at 5° C. withstirring. The mixture is stirred for 1 hour at 5° C. and then for 2hours at ambient temperature. The pyridine is distilled off in vacuum ona rotary evaporator. The residue is mixed with water and filtered undersuction. After washing with water, it is dried at 50° C. in vacuum.

Yield: 0.43 g (94% of theoretical),

Melting point: 242°-244° C.

C₂₀ N₂₃ N₂ O₄ (456.55), Calculated: C, 73.66; H, 6.18; N, 6.14. Found:C, 73.50; H, 6.20; N, 6.36.

Example 61 4'-(7-n-Butoxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate a) Tert.butyl 4'-(7-n-butoxy-2-n-butyl-4-methylbenzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

A mixture of 0.94 g (2 mmol) of tert.butyl 4'-(2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate,36 ml of dimethylformamide, 4 ml of water, 1.4 g (10 mmol) of potassiumcarbonate and 0.9 g (6.6 mmol) of n-butylbromide is stirred for 16 hoursat ambient temperature. The mixture is poured onto 200 ml of iced waterand the oily precipitate obtained is taken up in methylene chlorideafter being decanted off. The methylene chloride solution is dried oversodium sulphate and evaporated in vacuum. The crude product is purifiedover a silica gel column (grain size: 0.065-0.2 mm, eluting agent:methylene chloride/ethanol=50:1).

Yield: 0.8 g (76.2% of theoretical),

Oil, R_(f) value: 0.6 (silica gel: methylene chloride/ethanol=19:1)

C₂₄ H₄₂ N₂ O₃ (526.7), Calculated: C, 77.53; H, 8.04; N, 5.32. Found: C,77.53; H, 7.87; N, 5.31.

The following compounds are obtained in analogous manner:

tert.butyl 4'(2-n-butyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.70 (silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-7-(2-methoxyethoxy)-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.35 (Aluminium oxide plate: methylenechloride/ethanol=99:1)

b) 4'-(7-n-Butoxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

0.8 g (1.5 mmol) of tert.butyl 4'-(7-n-butoxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateare dissolved in 15 ml of methylene chloride, 5 ml of trifluoroaceticacid are added and the mixture is stirred for 2 hours at ambienttemperature. The product is rotary evaporated to dryness in vacuum andthe residue is recrystallised from acetone. The crystals are dried at50° C. in vacuum.

Yield: 0.45 g (51.3% of theoretical),

Melting point: 172°-174° C.

C₂₆ H₃₄ N₂ O₃ ×CF₃ COOH (584.65), Calculated: C, 65.74; H, 6.03; N,4.73. Found: C, 65.62; H, 6.15; N, 4.95.

The following compounds are obtained in analogous manner:

4'-(2-n-butyl-7-(2-(1-imidazolyl)-ethoxy)-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid bis-trifluoroacetate

melting point: 229°-231° C.

4'-(2-n-butyl-7-(2-hydroxyethoxy)-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

melting point: 216° C.

Example 62 4'-(2-n-Butyl-4-hydroxy-7-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 57 from 4-'-(4-benzyloxy-2-n-butyl-7-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid and hydrogen in methanol/dimethylformamide in the presence of 20%palladium hydroxide on carbon.

Yield: 64.4% of theoretical,

Melting point: 291°-294° C.

C₂₆ H₂₆ N₂ O₃ (414.51), Calculated: C, 75.34; H, 6.32; N, 6.76. Found:C, 75.22; H, 6.40; N, 6.64.

Example 63 4'-(2-Ethylsulphinylmethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

2.01 g (5.0 mmol) of 4'-(2-ethylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidare dissolved in 25 ml of glacial acetic acid and treated with 0.51 mlof 30% strength hydrogen peroxide. The solution is allowed to stand for24 hours at ambient temperature and is then evaporated to dryness. Theresidue is purified over a silica gel column (grain size: 40-63 μm,eluting agent: methylene chloride/ethanol/glacial aceticacid=50/1/0.15). The homogeneous fractions are combined, the solventsare distilled off, the residue is dissolved in methylene chloride andwashed three times using water. The organic phase is dried usingmagnesium sulphate and evaporated to dryness. The crystalline residue ismixed with diethylether, the mixture is filtered under suction and thecrystals are dried at 75° C. in vacuum.

Yield: 1.90 g (90.9% of theoretical), Melting point: 161°-163° C.

C₂₄ H₂₂ N₂ O₃ S (418.51), Calculated: C, 68.88; H, 5.30; N, 6.69; S,7.66. Found: C, 68.65; H, 5.40; N, 6.72; S, 7.64.

Example 64 4'-(2-n-Propylsulphinylmethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 63 from 4'-(2-n-propylthiomethyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid and hydrogen peroxide in glacial acetic acid.

Yield: 78.7% of theoretical,

Melting point: 128°-130° C.

C₂₃ H₂₄ N₂ O₃ S (432.54), Calculated: C, 69.42; H, 5.59; N, 6.48; S,7.41. Found: C, 69.57; H, 5.46; N, 6.04; S, 7.28.

Example 65 4'-(2-Hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid3-N-oxide

Prepared in analogous manner to Example 63 from 4'-(2-methylmercapto-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidand hydrogen peroxide in glacial acetic acid.

Yield: 35.9% of theoretical,

Melting point: 272°-274° C.

C₂₁ H₁₆ N₂ O₄ (360.37), Calculated: C, 69.99; H, 4.47; N, 7.77. Found:C, 70.00; H, 4.85; N, 7.51.

Example 66 4'-(2-Methylsulphinylmethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 63 from 4'-(2-methylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidand hydrogen peroxide/acetic acid.

Yield: 79.2% of theoretical,

Melting point: 232°-234° C.

C₂₃ H₂₀ N₂ O₃ S (404.48), Calculated: C, 68.30; H, 4.98; N, 6.93; S,7.93. Found: C, 68.17; H, 4.86; N, 7.04; S, 7.89.

Example 67 4'-(2-Ethylsulphonylmethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

2.01 g (5.0 mmol) of 4'-(2-ethylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidare dissolved in 25 ml of formic acid and 1.02 ml (10 mmol) of 30%strength hydrogen peroxide are added. The solution is allowed to standat ambient temperature for 24 hours and is then evaporated to dryness.The residue is purified over a silica gel column (grain size: 40-63 μm,eluting agent: methylene chloride/ethanol/glacial acetic acid=100/1/0.15to 50/1/0.15. The homogeneous fractions are combined and evaporated todryness. The residue is dissolved in methylene chloride, washed threetimes using water, the organic phase is dried using magnesium sulphateand evaporated to dryness. The crystalline residue is mixed withdiethylether, filtered under suction and dried at 75° C. in vacuum.

Yield: 1.80 g (82.9% of theoretical),

Melting point: 158°-160° C.

C₂₄ H₂₂ N₂ O₄ S (434.51), Calculated: C, 66.34; H, 5.10; N, 6.45; S,7.38. Found: C, 66.32; H, 5.05; N, 6.54; S, 7.27.

The following compounds are obtained in analogous manner:

4'-(2-n-butyl-6-methylsulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

4'-(2-n-butyl-6-ethylsulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

4'-(2-n-butyl-6-butylsulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Example 68 4'-(2-n-Propylsulphonylmethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 67 from 4'-(2-n-propylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid and hydrogen peroxide in formic acid.

Yield: 78.1% of theoretical,

Melting point: 135°-137° C.

C₂₃ H₂₄ N₃ O₄ S (448.54), Calculated: C, 66.95; H, 5.39; N, 6.25; S,7.15. Found: C, 66.83; H, 5.46; N, 6.03; S, 7.06.

Example 69 4'-(2-Methylsulphonylmethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 67 from 4'-(2-methylthiomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidand hydrogen peroxide.

Yield: 80.0% of theoretical,

Melting point: 290°-292° C.

C₂₃ H₂₀ N₂ O₄ S (420.43), Calculated: C, 65.70; H, 4.79; N, 6.66; S,7.62. Found: C, 65.67; H, 4.64; N, 6.88; S, 7.72.

Example 70 Ethyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

1.2 g (7 mmol) of 2-n-butyl-benzimidazole are dissolved in 25 ml ofdimethylsulphoxide, treated with 0.8 g (7 mmol) of potassiumtert.butoxide and the mixture is stirred for 20 minutes at ambienttemperature. 2.25 g (7 mmol) of2-carbethoxy-biphenyl-4'-yl-methylbromide are then added and the mixtureis stirred at ambient temperature until conversion is quantitative(about 1 hour). After pouring into 100 ml of iced water, the product isextracted 2 times using ethyl acetate, the combined organic extracts aredried over sodium sulphate and evaporated. The crude product obtained ispurified over a silica gel column (grain size: 0.04-0.2 mm, elutingagent: methylene chloride/ethanol=24.1).

Yield: 2.3 g (79.3% of theoretical),

Oil, R_(f) value: 0.6 (Silica gel: methylethylketone/xylene=1:1)

C₂₇ H₃₃ H₂ O₂ (412.53), Calculated: C, 78.41; H, 6.84; N, 6.79. Found:C, 78.43; H, 6.76; N, 7.01.

The following compound is obtained in analogous manner:

ethyl 4'-(2-n-butyl-7-n-butylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.50 (Silica gel: methylene chloride/ethanol=10:1)

Example 71 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 62.3% of theoretical,

Melting point: 214°-215° C.

C₂₃ H₂₄ N₃ O₂ (384.48), Calculated: C, 78.10; H, 6.29; N, 7.29. Found:C, 77.93; H, 6.21; N, 7.39.

Example 72 4'-(6-Benzylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

1.30 g (2.5 mmol) of ethyl 4'-(6-benzylamino-2-n-butylbenzimidazol-1-yl)-methyl!biphenyl-2-carboxylateare dissolved in 20 ml of ethanol, treated with 20 ml of 2N sodiumhydroxide and heated at reflux for 2 hours. After cooling to ambienttemperature, the solution is diluted to 500 ml using water and acidifiedto pH 5 using glacial acetic acid. The precipitate thus obtained isfiltered off once again under suction, suspended in acetone, filteredoff once again under suction and dried at 90° C. in vacuum.

Yield: 1.10 g (89.4% of theoretical),

Melting point: 250°-251° C.

C₂₃ H₂₁ H₃ O₂ (489.62), Calculated: C, 78.50; H, 6.38; N, 8.56. Found:C, 78.30; H, 6.49; N, 8.71.

The following compound is obtained in analogous manner:

4'-(2-n-butyl-7-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Melting point: 278°-279° C. (decomposition)

Example 73 4'-(2-n-Butyl-4-methyl-7-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hydrate

Prepared in analogous manner to Example 72 from methyl 4'-(2-n-butyl-4-methyl-7-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand 2N sodium hydroxide in ethanol.

Yield: 55.1% of theoretical,

Melting point: 313°-315° C.

C₂₉ H₃₀ N₂ O₃ ×H₂ O (432.52), Calculated: C, 72.20; H, 6.83; N, 6.43.Found: C, 72.43; H, 6.30; N, 6.34.

Example 74 Tert.butyl 4'-(2-n-butyl-4-methyl-7-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Prepared in analogous manner to Example 57 from tert.butyl 4'-(2-n-butyl-4-methyl-7-benzyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand hydrogen in the presence of palladium hydroxide on carbon inmethanol.

Yield: 80.0% of theoretical,

Melting point: 214°-216° C.

C₃₃ H₃₄ N₂ O₃ (470.62), Calculated: C, 76.57; H, 7.28; N, 5.95. Found:C, 76.83; H, 7.12; N, 6.00.

Example 75 Tert.butyl 4'-(2-n-Butyl-7-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidhydrate

Prepared in analogous manner to Example 56 from 3-amino-2-(2-tert.butoxycarbonyl-biphenyl-4'yl)-methyl!aminotoluene and valericacid

Yield: 28.6% of theoretical,

Melting point: 231°-233° C.

C₂₀ H₂₀ N₂ O₂ ×H₂ O (416.52), Calculated: C, 74.98; H, 6.78; N, 6.73.Found: C, 74.89; H, 6.52; N, 6.85.

Example 76 4'-(6-Amino2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate acidditrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-amino-2-n-butyl-benzyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 72.5% of theoretical,

Melting point: 72°-74° C.

C₂₉ H₂₈ N₃ O₂ ×2CF₃ COOH (627.54), Calculated: C, 55.51; H, 4.34; N,6.70. Found: C, 55.70; H, 4.61; N, 6.55.

Example 77 4'-(5-Amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate acidditrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(5-amino-2-n-butyl-benzyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 45.9% of theoretical,

Melting point: 64°-66° C.

C₂₅ H₂₅ N₃ O₂ ×2CF₃ COOH (627.54), Calculated: C, 55.51; H, 4.34; N,6.70. Found: C, 55.66; H, 4.42; N, 6.54.

Example 78 4'-(2-n-Butyl-5-(n-butylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateacid semitrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-(n-butylaminocarbonylamino)-benzyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 84.2% of theoretical,

Melting point: 165°-167° C.

C₃₀ H₃₄ N₄ O₃ ×1/2CF₃ COOH (555.64), Calculated: C, 67.01; H, 6.26; N,10.08. Found: C, 66.88; H, 6.51; N, 9.89.

Example 79 4'-(2-n-Butyl-6-phenylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-phenylaminocarbonylamino)-benzyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 92.6% of theoretical,

Melting point: 281°-283° C.

C₃₂ H₃₀ N₄ O₃ (518.61), Calculated: C, 74.11; H, 5.83; N, 10.80. Found:C, 73.93; H, 5.83; N, 10.58.

Example 80 4'-(2-n-Butyl-6-cyclohexylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylaminocarbonylamino)-benzyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 86.5% of theoretical,

Melting point: 199°-200° C.

C₃₃ H₃₀ N₄ O₃ ×CF₃ COOH (638.68), Calculated: C, 63.94; H, 5.84; N,8.77. Found: C, 64.12; H, 6.15; N, 9.01.

Example 81 4'-(2-n-Butyl-5-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 93% of theoretical,

Melting point: 163°-165° C.

C₃₃ H₃₂ N₃ O₂ (469.59), Calculated: C, 74.18; H, 6.65; N, 8.95. Found:C, 74.13; H, 6.67; N, 8.74.

Example 82 4'-(2-(4-Hydroxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(4-hydroxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 87.3% of theoretical,

Melting point: 251°-253° C.

C₂₇ H₂₀ N₂ O₃ (420.47), Calculated: C, 77.13; H, 4.79; N, 6.66. Found:C, 76.98; H, 4.83; N, 6.62.

Example 83 4'-(2-(4-n-Butoxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(4-n-butoxyphenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 85.2% of theoretical,

Melting point: 246°-248° C.

C₃₁ H₂₆ N₂ O₃ (476.58), Calculated: C, 78.13; H, 5.92; N, 5.88. Found:C, 78.33; H, 5.76; N, 5.67.

Example 84 4'-(2-n-Butyl-6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 63.6% of theoretical,

Melting point: 220°-222° C.

C₂₅ H₂₃ ClN₂ O₂ (418.92), Calculated: C, 71.68; H, 5.53; N, 6.69; Cl,8.46. Found: C, 71.81; H, 5.64; N, 6.69; Cl, 8.39.

Example 85 4'-(2-n-Butyl-6-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 70.6% of theoretical,

Melting point: 219°-221° C.

C₂₆ H₂₈ N₂ O₂ (398.51), Calculated: C, 78.36; H, 6.58; N, 7.03. Found:C, 78.49; H, 6.53; N, 6.98.

Example 86 4'-(2-n-Butyl-5-methanesulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-methanesulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride

Yield: 75.7% of theoretical,

Melting point: 242°-244° C.

C₃₀ H₂₇ N₂ O₄ S (477.59), Calculated: C, 65.39; H, 5.70; N, 8.80; S,6.71. Found: C, 65.52; H, 5.65; N, 8.55; S, 6.51.

Example 87 4'-(7-n-Butanoyloxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 60 from 4'-(2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand butyric acid chloride in pyridine.

Yield: 29.1% of theoretical,

Melting point: 240°-242° C.

C₃₀ H₃₂ N₂ O₄ (484.60), Calculated: C, 74.63; H, 6.66; N, 5.78. Found:C, 74.20; H, 6.76; N, 5.87.

Example 88 4'-(2-n-Butyl-6-ethoxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-ethoxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 85.2% of theoretical,

Melting point: 240°-242° C.

C₂₅ H₂₃ N₃ O₃ (471.55), Calculated: C, 71.32; H, 6.20; N, 8.91. Found:C, 71.06; H, 6.36; N, 9.04.

Example 89 4'-(2-n-Butyl-6-isopropylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-isopropylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 91.5% of theoretical,

Melting point: 155°-157° C.

C₂₉ H₃₁ N₃ O₄ S (505.63), Calculated: C, 66.51; H, 6.18; N, 8.31; S,6.34. Found: C, 66.26; H, 6.33; N, 8.34; S, 6.43.

Example 90 4'-(2-n-Butyl-4-nitrobenzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-nitrobenzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 84.6% of theoretical,

Melting point: 238°-240° C.

C₂₅ H₂₃ N₃ O₄ (429.48), Calculated: C, 69.92; H, 5.40; N, 9.78. Found:C, 69.85; H, 5.43; N, 9.67.

Example 91 4'-(2-n-Butyl-4-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 96.1% of theoretical,

Melting point: 270°-271° C.

C₂₉ H₃₁ N₃ O₂ (469.58), Calculated: C, 74.18; H, 6.65; N, 8.95. Found:C, 74.02; H, 6.74; N, 8.90.

Example 92 4'-(2-n-Butyl-4-ethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-ethylamino-carbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 87.5% of theoretical,

Melting point: 344°-346° C.

C₂₆ H₂₈ N₄ O₃ (470.57), Calculated: C, 71.47; H, 6.43; N, 11.91. Found:C, 71.51; H, 6.29; N, 11.48.

Example 93 4'-(2-(3-Pyridyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(3-pyridyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 73.3% of theoretical,

Melting point: 249°-251° C.

C₂₆ H₁₈ N₃ O₂ (405.46), Calculated: C, 77.02; H, 4.72; N, 10.36. Found:C, 76.85; H, 4.72; N, 10.15.

Example 94 4'-(2-n-Butyl-5-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 58.7% of theoretical,

Melting point: 188°-190° C.

C₂₈ H₂₆ N₂ O₂ (398.51), Calculated: C, 78.36; H, 6.58; N, 7.03. Found:C, 78.21; H, 6.62; N, 6.98.

Example 95 4'-(2-n-Butyl-6-dimethylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-dimethylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 65.4% of theoretical,

C₂₇ H₂₉ N₃ O₅ ×CF₃ COOH (541.58), Calculated: C, 64.31; H, 5.59; N,7.76. Found: C, 64.53; H, 5.66; N, 7.09.

Example 96 4'-(2-n-Butyl-5-(tert.butoxycarbonylaminoacetamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 72 from ethyl 4'-(2-n-butyl-5-(tert.butoxycarbonylaminoacetamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand 2N sodium hydroxide.

Yield: 16.7% of theoretical,

Melting point: 149°-151° C.

C₂₃ H₃₀ N₄ O₃ (556.66), Calculated: C, 69.05; H, 6.52; N, 10.06. Found:C, 69.12; H, 6.32; N, 9.87.

Example 97 4'-(2-n-Butyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 17.5% of theoretical,

Melting point: 222°-225° C.

C₂₇ H₂₃ N₂ O₂ (412.50), Calculated: C, 78.62; H, 6.84; N, 6.79. Found:C, 78.36; H, 6.90; N, 6.83.

Example 98 4'-(2-(2,2-Dimethylpropyl)-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(2,2-dimethylpropyl)-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 45% of theoretical,

Melting point: from 115° C. (amorphous)

C₂₉ H₃₃ N₂ O₂ (426.60), Calculated: C, 78.83; H, 7.09; N, 6.57. Found:C, 78.64; H, 7.11; N, 6.89.

Example 99 4'-(2-n-Benzyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-benzyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 68% of theoretical,

Melting point: 252°-255° C.

C₃₀ H₂₆ N₂ O₃ (446.60), Calculated: C, 80.69; H, 5.87; N, 6.27. Found:C, 80.94; H, 5.76; N, 5.97.

Example 100 4'-(2-(2-Methylbutyl)-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(2-methylbutyl)-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 57% of theoretical,

Melting point: 211°-215° C.

C₂₈ H₂₅ N₂ O₂ (426.60), Calculated: C, 78.84; H, 7.09; N, 6.57. Found:C, 78.67; H, 7.24; N, 6.43.

Example 101 4'-(2-(Cyclohexylmethyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(cyclohexylmethyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 31% of theoretical,

Melting point: 199°-201° C.

C₃₀ H₂₈ N₂ O₂ (452.60), Calculated: C, 79.61; H, 7.13; N, 6.19. Found:C, 79.45; H, 7.17; N, 6.06.

Example 102 4'-(2-(Cyclohexylmethyl-5,6-dichloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-cyclohexylmethyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 39% of theoretical,

Melting point: 219°-222° C.

C₂₈ H₂₆ Cl₂ N₂ O₂ (493.40), Calculated: C, 68.16; H, 5.31; N, 5.68; Cl,14.37. Found: C, 67.97; H, 5.29; N, 5.52; Cl, 14.12.

Example 103 4'- (2-(2-Methylbutyl)-naphtho2,3-d!imidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(2-methylbutyl)-naphtho2,3-d!imidazol-1-yl)-methyl!biphenyl-2-carboxylate and trifluoroaceticacid in methylene chloride.

Yield: 64% of theoretical,

Melting point: 206°-208° C.

C₃₀ H₂₆ N₂ O₂ (448.60), Calculated: C, 80.33; H, 6.29; N, 6.25. Found:C, 80.20; H, 6.36; N, 6.24.

Example 104 4'- (2-n-Propyl-naphtho2,3-d!imidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-propyl-naphtho 2,3-d!imidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 85% of theoretical,

Melting point: 269°-272° C.

C₂₆ H₂₄ N₂ O₂ (420.50), Calculated: C, 79.98; H, 5.75; N, 6.66. Found:C, 79.87; H, 5.48; N, 6.48.

Example 105 4'-(2-n-Butyl-5,6-dichloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5,6-dichloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 50% of theoretical,

Melting point: 237°-239° C.

C₂₃ H₂₂ Cl₂ N₂ O₂ (453.40), Calculated: C, 66.23; H, 4.89; N, 6.18; Cl,15.64. Found: C, 66.10; H, 4.82; N, 6.05; Cl, 15.42.

Example 106 4'-(2-Cyclohexylmethyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-cyclohexylmethyl-5,6-dimethoxy-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 45% of theoretical,

Melting point: 245°-247° C.

C₃₀ H₂₂ N₂ O₄ (484.60), Calculated: C, 74.36; H, 6.66; N, 5.78. Found:C, 74.11; H, 6.58; N, 6.02.

Example 107 4'-(2-n-Butyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 52% of theoretical,

Melting point: 257°-259° C.

C₂₇ H₂₆ N₂ O₄ (444.50), Calculated: C, 72.95; H, 6.35; N, 6.30. Found:C, 72.77; H, 6.26; N, 6.49.

Example 108 4'-(2-Cyclopentylmethyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-cyclopentylmethyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 47% of theoretical,

Melting point: 233°-234° C.

C₂₆ H₂₀ N₂ O₄ (470.60), Calculated: C, 74.02; H, 6.43; N, 5.95. Found:C, 73.96; H, 6.56; N, 6.18.

Example 109 4'-(2-(3-Methylbutyl)-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(3-methylbutyl)-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 39% of theoretical,

Melting point: 237°-239° C.

C₂₈ H₂₄ N₃ O₄ (458.60), Calculated: C, 73.34; H, 6.59; N, 6.11. Found:C, 73.50; H, 6.48; N, 6.02.

Example 110 4'-(2-Cyclohexyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-cyclohexyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 27% of theoretical,

Melting point: 240°-242° C.

C₂₈ H₂₆ N₂ O₂ (438.60), Calculated: C, 79.42; H, 6.89; N, 6.39. Found:C, 79.30; H, 7.02; N, 6.39.

Example 111 4'-(2-(1-Butyn-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(1-butyn-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 55% of theoretical,

Melting point: 218°-221° C.

C₂₃ H₂₀ N₂ O₂ (380.50), Calculated: C, 78.93; H, 5.30; N, 7.36. Found:C, 78.97; H, 5.24; N, 7.31.

Example 112 4'-(2-Cyclopentyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-cyclopentyl-5,6-dimethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 75% of theoretical,

Melting point: 262°-265° C.

C₂₅ H₂₀ N₂ O₂ (424.50), Calculated: C, 79.22; H, 6.65; N, 6.60. Found:C, 78.99; H, 6.54; N, 6.67.

Example 113 4'- (2-n-Butyl-5- and6-fluoro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5- and6-fluoro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 80% of theoretical,

Melting point: 167°-169° C.

C₂₃ H₂₂ FN₂ O₂ (402.50), Calculated: C, 74.61; H, 5.76; N, 6.56. Found:C, 74.57; H, 5.77; N, 7.05.

Example 114 4'- (2-n-Butyl-5- and6-benzoyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-benzoyl-and6-benzoyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 58.5% of theoretical,

Melting point: 180°-182° C.

C₃₂ H₂₈ N₂ O₃ (488.50)

Calculated: C 78.67 H 5.78 N 5.73

Found: C 78.75 H 5.74 N 5.63

EXAMPLE 115 4'- (2-n-Butyl-5-and6-trifluoromethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-and6-trifluoromethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 65% of theoretical,

Melting point: 172°-174° C.

C₂₀ H₂₃ F₃ N₂ O₃ (452.50)

Calculated: C 69.01 H 5.12 N 6.19

Found: C 69.10 H 5.24 N 6.11

EXAMPLE 116 4'-(2-n-Butyl-4-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 72% of theoretical,

Melting point: 190°-192° C.

C₂₆ H₂₃ N₃ O₂ (409.49)

Calculated: C 76.26 H 5.66 N 10.62

Found: C 76.01 H 5.72 N 10.51

EXAMPLE 117 4'- (2-n-Butyl-5-and6-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-and6-n-butylamino-carbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 69% of theoretical,

Melting point: 88° C. (decomposition)

C₂₀ H₂₃ N₂ O₃ ×1/2 CF₃ COOH (483.60)

Calculated: C 68.88 H 6.25 N 7.77

Found: C 68.65 H 6.32 N 7.71

EXAMPLE 118 4'-(2-n-Butyl-6-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 91% of theoretical,

Melting point: 315°-320° C. (decomposition)

C₂₀ H₂₄ N₂ O₄ (428.50)

Calculated: C 72.88 H 5.65 N 6.54

Found: C 72.74 H 5.66 N 6.58

EXAMPLE 119 4'-(2-n-Butyl-5-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 63% of theoretical,

Melting point: 247°-248° C.

C₂₈ H₂₄ N₂ O₄ (428.50)

Calculated: C 72.88 H 5.65 N 6.54

Found: C 72.76 H 5.52 N 6.52

EXAMPLE 120 4'-(2-n-Butyl-6-aminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-aminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 45% of theoretical,

Melting point: 243°-244° C.

C₂₆ H₂₅ N₃ O₃ ×1/2 H₂ O (436.51)

Calculated: C 71.54 H 6.00 N 9.63

Found: C 71.34 H 6.16 N 9.45

EXAMPLE 121 4'-(2-n-Butyl-5-aminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-aminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 55% of theoretical,

Melting point: 227°-228° C.

C₂₆ H₂₅ N₃ O₃ ×1/2 H₂ O (436.51)

Calculated: C 71.54 H 6.00 N 9.63

Found: C 71.42 H 5.94 N 9.46

EXAMPLE 122 4'- (2-n-Butyl-5-and6-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-and6-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 70% of theoretical,

Melting point: 214°-215° C.

C₂₆ H₂₃ N₃ O₂ (409.50)

Calculated: C 76.26 H 5.66 N 10.26

Found: C 76.06 H 5.44 N 10.11

EXAMPLE 123 4'-(2-n-Butyl-5-(1H-tetrazol-5-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-(1H-tetrazol-5-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 66% of theoretical,

Melting point: 249°-250° C.

C₂₅ H₂₄ N₆ O₂ (452.50)

Calculated: C 69.01 H 5.35 N 18.57

Found: C 69.92 H 5.48 N 18.78

EXAMPLE 124 4'- (2-n-Butyl-5-and6-(1H-tetrazol-5-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-and6-(1H-tetrazol-5-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 55% of theoretical,

Melting point: 220° C. (decomposition)

C₂₆ H₂₄ N₈ O₂ (452.50)

Calculated: C 69.01 H 5.35 N 18.57

Found: C 68.92 H 5.41 N 18.35

EXAMPLE 125 Tert.butyl 4'-(2-n-butyl-5-dimethylaminosulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-dimethylaminosulphonyl-3-N-oxido-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateby catalytic hydrogenation in the presence of Raney nickel andsubsequent reaction with trifluoroacetic acid in methylene chloride.

Yield: 92% of theoretical,

Melting point: 240°-242° C.

C₂₇ H₂₈ N₃ O₄ S (491.60)

Calculated: C 65.97 H 5.95 N 8.55 S 6.52

Found: C 65.41 H 6.09 N 8.46 S 6.60

EXAMPLE 126 4'- (2-n-Butyl-5-and6-methoxycarbonylbenzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

0.71 g (1.0 mmol) of 4'- (2-n-butyl-5-and6-methoxycarbonyl-benzimidazol-1-yl)-methyl!-2-(1triphenylmethyl-tetrazol-5-yl)-biphenylare heated with 25 ml of 5% strength methanolic ammonia at 125°-130° C.for 16 hours in a pressure vessel. After cooling, the solvent isdistilled off, the residue is taken up in dilute acetic acid andextracted three times using ethyl acetate. The combined ethyl acetatephases are washed using sodium chloride solution, dried over sodiumsulphate, evaporated and the residue is purified over a silica gelcolumn using methylene chloride/ethanol=25:1 as eluting agent.

Yield: 0.34 g (73% of theoretical),

Melting point: 136°-138° C.

C₂₇ H₂₅ N₆ O₂ (466.56)

Calculated: C 69.50 H 5.57 N 17.98

Found: C 69.42 H 5.33 N 17.44

EXAMPLE 127 4'- (2-n-Butyl-5-and6-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

216 ng (1.05 mmol) of dicyclohexylcarbodiimide and 141 mg (1.05 mmol) of1-hydroxybenzotriazole hydrate are dissolved in 30 ml of acetonitrileand 452 mg (1.00 mmol) of 4'- (2-n-butyl-5-and6-carboxy-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl areadded.

After stirring for 30 minutes at ambient temperature, 146 mg (2.00 mmol)of n-butylamine are added and the reaction mixture is stirred for 4hours at ambient temperature. The dicyclohexylurea obtained is filteredoff and the filtrate is evaporated. The residue obtained is taken up inmethylene chloride and washed once using 5% strength sodium bicarbonatesolution and once using sodium chloride solution. After evaporating onceagain, the final product is obtained by chromatography on a silica gelcolumn (eluting agent: methylene chloride/ethanol=25:1).

Yield: 95 mg (19% of theoretical),

Melting point: 245°-247° C.

C₂₀ H₂₃ N₇ O (507.63)

Calculated: C 71.00 H 6.50 N 19.30

Found: C 70.77 H 6.66 N 19.36

EXAMPLE 128 4'- (2-n-Butyl-5-and6-aminocarbonyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 127 from 4'- (2-n-butyl-5-and6-carboxy-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl.

Yield: 17% of theoretical,

Melting point: 225°-227° C.

C₂₆ H₂₅ N₇ O (451.62)

Calculated: C 69.98 H 5.54 N 21.62

Found: C 69.85 H 5.30 N 21.48

EXAMPLE 129 4'- (2-n-Butyl-5-and6-hydroxymethyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

452 mg (1.00 mmol) of 4'- (2-n-butyl-5-and6-carboxy-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl aredissolved in 20 ml of tetrahydrofuran and 67.0 mg (1.75 mmol) of lithiumaluminium hydride are added. The suspension is stirred at 40° C. for 4hours and then separated using 20 ml of water/ethanol (1:1). Afterfiltering over kieselguhr, the product is evaporated and chromatographedon silica gel (eluting agent: methylene chloride/ethanol=9:1 with 1%ammonia added).

Yield: 90 mg (21% of theoretical),

Melting point: 173°-175° C.

C₂₆ H₂₆ N₆ O (438.54)

Calculated: C 71.50 H 5.96 N 19.20

Found: C 71.32 H 6.06 N 19.02

The following compound is obtained in analogous manner:

4'- (2-n-butyl-5-and6-(n-butylaminomethyl)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenylmelting point: 146°-149° C.

EXAMPLE 130 4'- (2-n-Butyl-5-and6-carboxy-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

2.1 g (3.0 mmol) of 4'- (2-n-butyl-5-and6-methoxycarbonyl-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenylare dissolved in 100 ml of ethanol while heating, treated at 40° C. with25 ml of 1N sodium hydroxide and stirred at ambient temperature of 60hours. The reaction solution is evaporated, the residue obtained isdissolved in iced water and brought to pH 4-5 using 2N acetic acid. Thecrude product precipitated is filtered off under suction, washed untilit is neutral using water and purified over a silica gel column (elutingagent: methylene chloride/ethanol=9:1 with 1% of glacial acetic acidadded).

Yield: 0.65 g (48% of theoretical),

Melting point: 188°-190° C.

C₂₈ H₂₄ N₆ O₂ (452.60)

Calculated: C 68.80 H 5.53 N 18.52

Found: C 68.63 H 5.34 N 18.65

EXAMPLE 131 4'-(2-n-Butyl-7-cyano-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-7-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 68% of theoretical,

Melting point: 190°-192° C.

C₂₈ H₂₃ N₃ O₂ (409.49)

Calculated: C 76.26 H 5.66 N 10.26

Found: C 75.99 H 5.46 N 10.25

EXAMPLE 132 4'-(2-n-Butyl-5,7-difluoro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5,7-difluoro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 49% of theoretical,

Melting point: from 155° C. (amorphous)

C₂₅ H₂₂ F₂ N₂ O₂ (420.40)

Calculated: C 71.41 H 5.27 N 6.66

Found: C 71.38 H 5.09 N 6.39

EXAMPLE 133 4'-(2-n-Butyl-5-acetyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-acetyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 59.5% of theoretical,

Melting point: 182°-184° C.

C₂₇ H₂₈ N₂ O₃ (426.50)

Calculated: C 76.03 H 6.14 N 6.57

Found: C 75.89 H 6.35 N 6.33

EXAMPLE 134 4'-(2-Cyclohexylmethyl-5,6-dihydroxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid

0.29 ml (3 mmol) of boron tribromide is added dropwise to a suspensionof 242 mg (0.5 mmol) of 4'-(2-cyclohexylmethyl-5,6-dihydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid in 25 ml of dichloromethane at -5° C. When the addition iscomplete, the cooling bath is removed and the mixture is stirred atambient temperature for 5 hours. 20 ml of methanol are then added whilethe mixture is cooled with ice, then the reaction mixture is evaporatedto dryness and the residue is suspended in 10 ml of water whilestirring.

The crude product precipitated is filtered off under suction, washedwith a further 10 ml of water, dried and chromatographed over a silicagel column (eluting agent: dichloromethane/ethanol=9:1).

Yield: 51 mg (22% of theoretical),

Melting point: amorphous

C₂₈ H₂₈ N₂ O₄ (456.50)

Calculated: C 73.66 H 6.18 N 6.14

Found: C 73.79 H 6.31 N 6.22

The following compounds are obtained in analogous manner:

4'- (2-n-butyl-5-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

melting point: 306°-307° C.

4'- (2-n-butyl-4-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

melting point: 292°-293° C.

4'- (2-n-butyl-7-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

melting point: 295°-297° C.

EXAMPLE 135 4'-(2-(3-Methylbutyl)-5-methoxy-6-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid and 4'-(2-(3-methylbutyl)-5-hydroxy-6-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

3 g of aluminium trichloride are added to a suspension of 600 mg (1.3mmol) of 4'-(2-(3-methylbutyl)-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid in 50 ml of dry dichloromethane and the mixture is heated underreflux for 15 minutes. The solvent is then distilled off, the residue isfiltered off under suction, washed using 30 ml of water and dried. 360mg (62% of theoretical) of a mixture of the isomeric products isobtained after chromatographing over silica gel (eluting agent:dichloromethane/ethanol=9:1).

To separate the isomers, 230 mg of the mixture are chromatographed againover silica gel (eluting agent: dichloromethane/ethanol=11:1). 80 mg of4'-(2-(3-methylbutyl)-5-methoxy-6-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid (melting point: 189°-192° C.)

C₂₇ H₂₈ N₂ O₄ (444.50)

Calculated: C 72.95 H 6.35 N 6.30

Found: C 72.84 H 6.32 N 6.19

and 30 mg of 4'-(2-(3-methylbutyl)-5-hydroxy-6-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid (melting point: 188°-190° C.)

C₂₇ H₂₈ N₂ O₄ (444.50)

Calculated: C 72.95 H 6.35 N 6.30

Found: C 73.13 H 6.39 N 6.41

are thus obtained.

EXAMPLE 136 Ethyl 4'-(2-n-butyl-7-n-propylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

2.0 g (4.7 mmol) of ethyl 4'-(7-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate aredissolved in 50 ml of ethanol and 0.53 ml (7.5 mmol) of propionaldehydeand 0.05 g of 10% palladium on carbon are added and the mixture ishydrogenated for 2 hours at ambient temperature and 5 bar hydrogenpressure. The catalyst is then filtered off under suction and thesolvent is removed in vacuum. The oily residue is purified over analuminium oxide column (neutral, activity II-III), the column beingeluted with cyclohexane/methylene chloride=3:1 and 1:1. The appropriatefractions are combined and rotary evaporated.

Yield: 2.0 g (90.9% of theoretical), oil, R_(f) value: 0.050 (Silicagel: methylene chloride/ethanol)=19:1

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-n-butyl-5-n-pentylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylate

R_(f) value: 0.45 (Aluminium oxide, methylene chloride)

tert.butyl 4'-(2-n-butyl-6-n-pentylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.40 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-6-n-butylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.50 (Silica gel: methylethylketone/xylene=1:1)

tert.butyl 4'-(2-n-butyl-6-(2-cyclohexyl-ethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.40 (Silica gel: ethyl acetate/petroleum ether=60:40)

tert.butyl 4'- (2-n-butyl-6-(cis-andtrans-decahydronaphth-2-yl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

oil, R_(f) value: 0.65 (Aluminium oxide plate: petroleum ether/ethylacetate=9:1)

EXAMPLE 137 4'-(2-n-Butyl-7-n-propylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 72 from ethyl 4'-(2-n-butyl-7-n-propylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand 2N sodium hydroxide/ethanol.

Yield: 85.7% of theoretical,

Melting point: 262°-263° C.

C₂₈ H₃₁ N₃ O₂ (441.57)

Calculated: C 76.16 H 7.08 N 9.52

Found: C 76.35 H 7.26 N 9.60

EXAMPLE 138 4'- (2-n-Butyl-5-and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-and6-nitro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 54.4% of theoretical,

Melting point: 223°-224° C.

C₂₃ H₂₃ N₃ O₄ (429.48)

Calculated: C 69.92 H 5.60 N 9.78

Found: C 69.81 H 5.47 N 9.72

EXAMPLE 139 4'-(2-n-Butyl-7-n-butylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 72 from ethyl 4'-(2-n-butyl-7-n-butylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand sodium hydroxide in ethanol.

Yield: 94.7% of theoretical,

Melting point: 225°-226° C.

C₂₈ H₂₃ N₃ O₄ S (519.66)

Calculated: C 67.03 H 6.40 N 8.09 S 6.17

Found: C 66.92 H 6.63 N 8.09 S 5.91

EXAMPLE 140 4'-(2-n-Butyl-5-n-pentylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-n-pentylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 92.3% of theoretical,

Melting point: 155°-157° C.

C₃₀ H₂₅ N₃ O₄ ×1/2 CF₃ COOH (526.64)

Calculated: C 70.70 H 6.79 N 7.98

Found: C 70.84 H 6.94 N 8.05

EXAMPLE 141 4'-(2-n-Butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-amino-biphenyl

2 g (3.2 mmol) of 4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-phthalimino-biphenylare dissolved in 20 ml of methanol and 10 ml of dimethylformamide and,after adding 20 ml of 40% strength methylamino solution, are stirred for2 hours at ambient temperature. The mixture is evaporated to dryness invacuum. The remaining residue is suspended in ether and the insolubleN-methyl-phthalimide is filtered off. The filtrate is evaporated todryness in vacuum and purified over silica gel (grain size: 0.063-0.2mm, eluting agent: methylene chloride with 0.5-2% ethanol). Theresulting product is suspended in ether, filtered under suction, washedusing ether and dried in vacuum.

Yield: 1.37 g (85.6% of theoretical),

Melting point: 209°-211° C.

C₃₁ H₂₇ N₅ O (495.68)

Calculated: C 75.12 H 7.52 N 14.13

Found: C 75.33 H 7.57 N 14.01

The following compound is obtained in analogous manner:

4'-(2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-amino-biphenyl

melting point: 249°-250° C.

EXAMPLE 142 4'-(2-n-Butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-aminomethyl-biphenyl

3.3 g (7.1 mmol) of 4'-(7-benzyloxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!-2-cyano-biphenylare dissolved in 100 ml of methanol and hydrogenated at ambienttemperature in the presence of 0.5 g of palladium (10% on carbon) at 5bar of hydrogen. After 3 hours the catalyst is filtered off. 20 ml of20% strength ammonia in methanol is added to the filtrate and themixture is hydrogenated again at 70° C. in the presence of 0.5 g ofRaney nickel at 5 bar of hydrogen. After 4 hours of the catalyst isfiltered off under suction and the filtrate is evaporated to dryness invacuum. The crude crystalline product is suspended in ether, filteredunder suction, washed using ether and dried in vacuum.

Yield: 2.6 g (92.8% of theoretical),

Melting point: 207°-212° C.

C₂₈ H₂₉ N₃ O (399.53)

Calculated: C 78.16 H 7.32 N 10.52

Found: C 77.97 H 7.34 N 10.51

EXAMPLE 143 4'-(2-n-Butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl)!-2-trifluoroacetamino-biphenyl

0.35 g (0.7 mmol) of 4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl)!-2-amino-biphenyl,dissolved in 15 ml of methylene chloride and 0.85 ml (6.1 mmol) oftriethylamine, is cooled to -60° C. and 0.85 ml of trifluoroaceticanhydride in 2 ml of methylene chloride is added dropwise whilestirring. The mixture is allowed to rise to ambient temperatureovernight and is evaporated to dryness. The residue is purified oversilica gel (eluting agent: methylene chloride with 0.5-2% ethanol. Theeluates collected are evaporated, crystallised from ether/benzene60°-80° C. and dried in vacuum.

Yield: 0.21 g (50% of theoretical),

Melting point: 231°-233° C.

C₃₃ H₃₆ F₃ N₅ O₂ (591.68)

Calculated: C 66.99 H 6.13 N 11.83

Found: C 66.83 H 5.96 N 11.71

The following compounds are obtained in analogous manner:

4'-(7-benzyloxy-2-n-butyl-4-methyl-benzimidazol-1-yl)-methyl!-2-trifluoroacetamino-biphenyl

melting point: 147°-149° C.

4'-(2-n-butyl-7-hydroxy-4-methyl-benzimidazol-1-yl)-methyl!-2-trifluoroacetaminomethyl-biphenyl

melting point: 247°-249° C.

4'-(7-benzyloxy-2n-butyl-4-methyl-benzimidazol-1-yl)-methyl!-2-trifluoromethanesulphonamino-biphenyl

oil, R_(f) value: 0.65 (Silica gel: petroleum ether/ethyl acetate=1:1)

4'-(2-n-butyl-7-trifluoromethanesulphonyloxy-4-methyl-benzimidazol-1-yl)-methyl!-2-trifluoromethanesulphonaminomethyl-biphenyl

melting point: 137°-139° C.

EXAMPLE 144 4'-(2-n-Butyl-4-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 76.5% of theoretical,

Melting point: 179°-181° C.

C₂₆ H₂₅ N₂ O₃ (414.51)

Calculated: C 75.34 H 6.32 N 6.76

Found: C 75.07 H 6.35 N 6.71

EXAMPLE 145 4'-(2-n-Butyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 80% of theoretical,

Melting point: 260°-261° C.

C₂₀ H₂₃ N₂ O₃ (414.51)

Calculated: C 75.34 H 6.32 N 6.76

Found: C 75.09 H 6.37 N 6.79

EXAMPLE 146 4'-(5-Aminoacetamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(5-aminoacetamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 40% of theoretical,

Melting point: 230°-232° C.

C₂₇ H₂₈ N₄ O₃ (456.54)

Calculated: C 71.03 H 6.18 N 12.27

Found: C 70.83 H 6.36 N 11.98

EXAMPLE 147 4'-(2-n-Butyl-5-n-pentylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-n-pentylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 92.3% of theoretical,

Melting point: 155°-157° C. (decomposition)

C₃₀ H₃₅ N₃ O₂ ×1/2 CF₃ COOH (526.64)

Calculated: C 70.70 H 6.79 N 7.98

Found: C 71.04 H 7.14 N 8.05

EXAMPLE 148 4'-(2-n-Butyl-6-methylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-methylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 77.3% of theoretical,

Melting point: 197°-199° C.

C₂₆ H₂₇ N₃ O₂ ×1/2 CF₃ COOH (470.53)

Calculated: C 68.92 H 5.89 N 8.93

Found: C 68.82 H 5.80 N 8.62

EXAMPLE 149 4'-(2-n-Butyl-6-(N-butanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-butanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 70.3% of theoretical,

Melting point: 165°-167° C.

C₃₀ H₃₃ N₃ O₃ (483.62)

Calculated: C 74.51 H 6.87 N 8.68

Found: C 74.51 H 6.89 N 8.56

EXAMPLE 150 4'-(6-Aminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-aminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 93.8% of theoretical,

Melting point: 134°-136° C.

C₂₀ H₃₀ N₄ O₃ ×CF₃ COOH (556.54)

Calculated: C 60.43 H 4.89 N 10.07

Found: C 60.22 H 4.87 N 9.80

EXAMPLE 151 4'-(2-n-Butyl-6-(n-hexylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(n-hexylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 93.3% of theoretical,

Melting point: 138°-140° C.

C₃₂ H₃₈ N₄ O₃ ×CF₃ COOH (640.70)

Calculated: C 63.74 H 6.14 N 8.74

Found: C 63.66 H 6.19 N 8.51

EXAMPLE 152 4'-(2-n-Butyl-4-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 72.5% of theoretical,

Melting point: 292°-293° C.

C₂₃ H₂₄ N₂ O₃ (400.48)

Calculated: C 74.98 H 6.04 N 7.00

Found: C 74.85 H 6.13 N 6.91

EXAMPLE 153 4'-(2-n-Butyl-5-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 81.1% of theoretical,

Melting point: 176°-177° C. (amorphous)

C₃₂ H₃₆ N₄ O₃ ×CF₃ COOH (638.69)

Calculated: C 63.94 H 5.84 N 8.77

Found: C 64.04 H 6.00 N 9.05

EXAMPLE 154 4'-(2-n-Butyl-7-isopropylaminomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-7-isopropylaminomethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 53% of theoretical,

Melting point: 156°-158° C.

C₂₈ H₂₃ N₃ O₃ ×H₂ O (473.61)

Calculated: C 73.54 H 7.45 N 8.87

Found: C 73.69 H 7.37 N 8.91

EXAMPLE 155 4'-(6-Aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hemi-hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 80.4% of theoretical,

Melting point: 147°-149° C.

C₂₆ H₂₈ N₄ O₂ S×1/2 H₂ O (467.58)

Calculated: C 66.80 H 5.81 N 6.85

Found: C 66.92 H 5.91 N 6.66

EXAMPLE 156 4'-(2-n-Butyl-6-cyclohexylaminothiocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylaminothiocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 88.2% of theoretical,

Melting point: 223°-225° C. (decomposition)

C₂₂ H₂₈ N₄ O₂ S (540.72)

Calculated: C 71.08 H 6.71 N 10.36 S 5.93

Found: C 70.95 H 6.77 N 10.53 S 6.23

EXAMPLE 157 4'-(2-n-Butyl-6-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-hydroxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 76.5% of theoretical,

Melting point: 264°-266° C.

C₂₅ H₂₄ N₂ O₃ (400.48)

Calculated: C 74.98 H 6.04 N 7.00

Found: C 75.06 H 5.95 N 6.98

EXAMPLE 158 4'-(2-n-Butyl-7-(2-methoxy-ethoxy)-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-7-(2-methoxy-ethoxy)-4-methyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 63.6% of theoretical,

Melting point: 205°-207° C.

C₂₀ H₂₃ N₂ O₄ (472.58)

Calculated: C 73.71 H 6.82 N 5.93

Found: C 73.48 H 6.64 N 6.15

EXAMPLE 159 4'-(2-n-Butyl-6-trifluoroacetylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-trifluoroacetylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 69.6% of theoretical, Melting point: 84°-86° C. C₂₇ H₂₄ N₃ O₃ F₃(495.50) Calculated: C 65.45, H 4.88, N 8.48 Found: 65.20, 5.06, 8.64

EXAMPLE 160 4'-(2-n-Butyl-4-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-4-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 94.4% of theoretical, Melting point: 242°-244° C. (decomposition)C₂₂ H₂₄ N₄ O₃ (524.66) Calculated: C 73.26, H 6.92, N 10.68 Found:72.42, 6.93, 10.77

EXAMPLE 161 4'-(6-Allylaminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-allylaminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2carboxylateand trifluoroacetic acid

Yield: 96% of theoretical, Melting point: 90°-92° C. C₂₀ H₃₀ N₄ O₃ x CF₃COOH (596.61) Calculated: C 62.41, H 5.24, N 9.39 Found: 62.20, 5.17,9.13

EXAMPLE 162 4'-(6-Benzylaminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-benzylaminocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 79.4% of theoretical, Melting point: 244°-245° C. C₃₃ H₂₃ N₄ O₃(532.64) Calculated: C 74.41, H 6.06, N 10.52 Found: 74.32, 6.09, 10.31

EXAMPLE 163 4'-(2-n-Butyl-6-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 54% of theoretical, Melting point: 149°-152° C. C₂₃ H_(H) ₃₃ N₄O₃ (526.68) Calculated: C 72.98, H 7.27, N 10.64 Found: 72.95, 7.27,10.73

EXAMPLE 164 4'-(5-Aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hydrochloride

Prepared in analogous manner to Example 9 from tert.butyl 4'-(5-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 66.6% of theoretical, Melting point: 150°-152° C. C₂₆ H₂₇ N₄ O₂SCl (495.04) Calculated: C 63.08, H 5.49, N 11.31, S 6.46 Found: 62.83,5.76, 11.15, 6.22

EXAMPLE 165 4'-(2-n-Butyl-5-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 64.6% of theoretical, Melting point: 229°-230° C. C₂₆ H₂₅ N₃ O₃(427.51) Calculated: C 73.05, H 5.89, N 9.83 Found: 73.31, 6.11, 9.58

EXAMPLE 166 4'-(2-n-Butyl-5-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 77.8% of theoretical, Melting point: 178°-180° C. C₂₉ H₃₁ N₃ O₂(469.59) Calculated: C 74.18, H 6.65, N 8.95 Found: 73.93, 6.70, 9.07

EXAMPLE 167 4'-(2-n-Butyl-6-(N-methylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid. Yield: 85.7% of theoretical, Melting point:163°-165° C. C₂₉ H₃₀ N₄ O₃ (470.58) Calculated: C 71.46, H 6.42, N 11.91Found: 71.33, 6.64, 11.74

EXAMPLE 168 4'-(2-n-Butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 90% of theoretical, Melting point: 145°-147° C. C₃₁ H₃₀ N₄ O₃(512.65) Calculated: C 72.64, H 7.08, N 10.93 Found: 72.90, 7.16, 10.69

EXAMPLE 169 4'-(2-n-Butyl-5-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 75% of theoretical, Melting point: 240°-242° C. C₃₂ H₃₀ N₄ O₃(526.69) Calculated: C 72.97, H 7.27, N 10.64 Found: 72.78, 7.23, 10.66

EXAMPLE 170 4'-(2-n-Butyl-6-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 53.7% of theoretical, Melting point: 152°-154° C. C₂₉ H₃₁ N₃ O₃(469.59) Calculated: C 74.16, H 6.65, N 8.95 Found: 73.96, 6.53, 8.97

EXAMPLE 171 4'-(6-Acetamino-2-n-butyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-acetamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 87% of theoretical, Melting point: 252°-254° C. C₃₇ H₂₇ N₃ O₃(441.53) Calculated: C 73.45, H 6.16, N 9.52 Found: 73.28, 5.95, 9.39

EXAMPLE 172 4'-(2-n-Butyl-6-propionylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-propionylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 90% of theoretical, Melting point: 269°-271° C. C₂₆ H₂₉ N₃ O₃(455.56) Calculated: C 73.82, H 6.42, N 9.22 Found: 73.99, 6.42, 9.18

EXAMPLE 173 4'-(6-n-Butanoylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-n-butanoyl-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 79.1% of theoretical, Melting point: 253°-255° C. C₂₉ H₃₁ N₃ O₃(469.58) Calculated: C 74.18, H 6.6, N 8.96 Found: 73.99, 6.65, 8.87

EXAMPLE 174 4'-(2-n-Butyl-6-(n-butylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(n-butylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 69.2% of theoretical, Melting point: 239°-242° C. C₃₀ H₃₄ N₄ O₃(498.62) Calculated: C 72.27, H 6.87, N 11.24 Found: 71.92, 6.86, 10.93

EXAMPLE 175 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonylmethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonylmethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 80% of theoretical, Melting point: 215°-217° C. C₃₃ H₃₃ N₄ O₃(538.69) Calculated: C 73.58, H 7.11, N 10.40 Found: 73.52, 7.19, 10.54

EXAMPLE 176 4'-(2-n-Butyl-6-(N-(dimethylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 66% of theoretical, Melting point: 224°-226° C. C₂₉ H₂₂ N₄ O₃(484.60) Calculated: C 71.88, H 6.66, N 11.56 Found: 71.61, 6.92, 11.27

EXAMPLE 177 4'-(2-n-Butyl-6-n-pentanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-n-pentanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 74.5% of theoretical, Melting point: 253°-255° C. C₃₀ H₃₃ N₃ O₃(483.61) Calculated: C 74.57, H 6.88, N 8.70 Found: 74.23, 7.08, 8.63

EXAMPLE 178 4'-(2n-Butyl-6-(N-(dimethylaminocarbonyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 83.1% of theoretical, Melting point: 198°-200° C. C₂₈ H₃₀ N₄ O₃ xCF₃ COOH (584.60) Calculated: C 61.63, H 5.34, N 9.58 Found: 61.62,5.50, 9.68

EXAMPLE 179 4'-(2-n-Butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacidtrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 70% of theoretical, Melting point: 152°-154° C. C₃₁ H₃₀ N₄ O₃ xCF₃ COOH (626.68) Calculated: C 63.25, H 5.95, N 8.94 Found: 63.18,6.07, 9.03

EXAMPLE 180 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-n-pentyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 46.7% of theoretical, Melting point: 134°-137° C. C₃₇ H₄₆ N₄ O₃(594.80) Calculated: C 74.72, H 7.79 N 9.62 Found: 74.52, 7.85, 9.34

EXAMPLE 181 Tert.butyl 4'-(2-n-butyl-6-(N-acetyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

4.5 g (9 mmol) of tert.butyl 4'-(2-n-butyl-6-actylamino-benzimidazol-1-yl)-methyl!biphenyl-3-carboxylateare dissolved in 50 ml of dimethylformamide and 0.48 g (9 mmol+10%) ofsodium hydride suspension in oil (50% strength) is added. The reactionmixture is stirred for 30 minutes at 80° C., cooled to ambienttemperature and treated with 1.5 g of methyl iodide (9 mmol+20%). Whenthe reaction is completed, the mixture is evaporated in vacuum, taken upin ethyl acetate and washed using water. The organic phase is dried oversodium sulphate and evaporated in vacuum, a oily residue being obtained.A yellowish oil is obtained after purifying over a silica gel column(grain size: 0.02-0.5 mm, eluting agent: methylenechloride/ethanol=49:1, 24:1).

Yield: 3.7 g (80.4% of theoretical), oil, R_(f) value: 0.75 (silica gel:methylene chloride/ethanol=19:1) C₂₃ N₃₇ N₃ O₃ (511.66) Calculated: C75.12, H 7.29, N 8.21 Found: 74.99, 7.32, 8.22

The following compounds are prepared in analogous manner:

tert.butyl 4'-(2-n-butyl-5-(N-propionyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.80 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

tert.butyl 4'-(2-n-butyl-6-(N-propionyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.65 (Silica gel: methylene chloride/ethanol=19:1)

EXAMPLE 182 4'-(2-n-Butyl-6-(tetrahydropyran-2-yl-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 7 from 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidand tetrahydropyran-2-yl-isocyanate.

Yield: 35.7% of theoretical, Melting point: 172°-174° C. C₃₁ H₃₄ N₄ O₄(562.64) Calculated: C 70.70, H 6.51, N 10.64 Found: 70.59, 6.77, 10.86

EXAMPLE 183 4'-(2-n-Butyl-6-phenylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hemi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-phenylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 29.2% of theoretical, Melting point: 273°-275° C. (decomposition)C₂₃ H₃₁ N₃ O₃ x 0.5 CF₃ COOH (574.64) Calculated: C 71.07, H 5.53, N7.31 Found: 71.01, 5.60, 7.11

EXAMPLE 184 4'-(2-n-Butyl-6-(N-(n-hexylaminocarbonyl)-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 97.1% of theoretical, Melting point: 196°-197° C. C₁₆ H₄₈ N₄ O₃(608.82) Calculated: C 74.97, H 7.95, N 9.20 Found: 74.75, 7.92, 9.19

EXAMPLE 185 4'-(2-n-Butyl-6-cyclohexylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 68.4% of theoretical, Melting point: 298°-300° C. (decomposition)C₂₂ H₂₅ N₃ O₄ (509.65) Calculated: C 75.41, H 6.92, N 8.24 Found: 75.38,6.78, 8.11

EXAMPLE 186 4'-(6-Benzyloxycarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(6-benzyloxycarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 64.9% of theoretical, Melting point: 238°-240° C. (decomposition)C₂₃ H₃₁ N₂ O₄ (533.63) Calculated: C 74.28, H 5.86, N 7.87 Found: 74.14,5.97, 7.72

EXAMPLE 187 4'-(2-n-Butyl-6-(2-cyclohexyl-ethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(2-cyclohexyl-ethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 66.6% of theoretical, Melting point: 217°-219° C. C₂₃ H₃₀ N₃ O₂(509.69) Calculated: C 77.77, H 7.71, N 8.24 Found: 77.57, 7.56, 8.23

EXAMPLE 188 4'-(2-n-Butyl-6-cyclohexylmethylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'(2-n-butyl-6-cyclohexylmethylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 80.4% of theoretical, Melting point: 239°-241° C. C₃₃ H₃₇ N₂ O₂(523.67) Calculated: C 75.69, H 7.12, N 8.02 Found: 75.53, 6.94, 7.97

EXAMPLE 189 4'-(2-n-Butyl-6-cyclohexylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylamino-carbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid

Yield: 89.2% of theoretical, Melting point: 305°-308° C. (decomposition)C₂₃ H₃₃ N₂ O₃ (509.65) Calculated: C 75.42, H 6.92, N 8.24 Found: 75.31,7.03, 8.11

EXAMPLE 190 4'-(2-n-Butyl-6-(N-methyl-n-butylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-methyl-n-butylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid

Yield: 94.5% of theoretical, Melting point: 176°-178° C. C₃₁ H₂₅ N₃ O₃(497.64) Calculated: C 74.82, H 7.09, N 8.44 Found: 74.98, 7.21, 8.50

EXAMPLE 191 4'-(2-n-Butyl-6-ethoxycarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-ethoxycarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 59.7% of theoretical, Melting point: 219°-220° C. C₂₃ H₂₆ N₃ O₄(456.54) Calculated: C 73.66, H 6.18, N 6.14 Found: 73.49, 6.13, 5.94

EXAMPLE 192 4'-(2-n-Butyl-5-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-5-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid

Yield: 48.9% of theoretical Melting point: 209°-210° C. C₃₀ H₂₃ N₃ O₃(483.61) Calculated: C 74.51, H 6.88, N 8.69 Found: 74.54, 6.79, 8.79

EXAMPLE 193 4'-(2-n-Butyl-6-(3-cyclohexyl-piperidino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid sesquitrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3-cyclohexyl-piperidino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 85.0% of theoretical Melting point: 155°-157° C. C₂₆ H₄₃ N₃ O₂ x1.5 CF₃ COOH (720.80) Calculated: C 64.99, H 6.22 N 5.83 Found: 64.88,6.41, 5.95

EXAMPLE 194 4'- (2-n-Butyl-6-(cis- andtrans-decahydronaphth-2-ylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid dihydrochloride

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis- andtrans-decahydronaphth-2-ylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 24.0% of theoretical, Melting point: from 132° C. C₃₅ H₄₁ H₃ O₂ x2 HCl (608.65) Calculated: C 69.07, H 7.12, N 6.90 Found: 68.98, 7.23,6.97

EXAMPLE 195 4'-(2-n-Butyl-6-cyclohexylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid sesquitrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 99.0% of theoretical, Melting point: 64°-66° C. (amorphous) C₃₁H₆₄ H₃ O₂ x 1.5 CF₃ COOH (652.68) Calculated: C 62.57, H 5.64, N 6.44Found: 62.68, 5.81, 6.25

EXAMPLE 196 4'-(2-n-Butyl-6-(2-isopropyl-5-methyl-cyclohexyloxycarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(2-isopropyl-5-methyl-cyclohexyloxycarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 94.1% of theoretical, Melting point: 149°-151° C. C₂₈ H₄₂ N₃ O₄ x0.5 CF₃ COOH (638.77) Calculated: C 69.57, H 6.86, N 6.58 Found: 69.39,6.91, 6.56

EXAMPLE 197 4'-(2-n-Butyl-6-cyclohexylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

EXAMPLE 198 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

960 mg (2.5 mmol) of 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid aredissolved in 25 ml of methylene chloride, treated with 2 ml of thionylchloride and heated under reflux for one hour. The solvent is thendistilled off and evaporated 2 times after adding methylene chloride.390 mg (2.5 mmol) of benzenesulphonamide are added to the residue andthe mixture is heated for one hour at 140° C. After cooling, the oilobtained is taken up in ethyl acetate/sodium chloride solution andextracted 3 times using ethyl acetate. The combined ethyl acetate phasesare dried over sodium sulphate, evaporated and the crude productobtained is purified over a silica gel column using methylenechloride/ethanol as eluting agent.

Yield: 0.15 g (11% of theoretical), Melting point: 131°-132° C. C₃₁ H₂₉N₃ O₃ S (523.65) Calculated: C 71.11, H 5.58, N 8.02 Found: 70.96, 5.49,8.21

The following compounds are obtained in analogous manner:

4'-(2-n-butyl-6-methoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-methoxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-pentyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-4-methyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-propyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-acetamino-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-butyl-5-chloro-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-butylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-phenylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-butyl-6-chloro-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-methanesulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-ethoxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-isopropylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-4-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-dimethylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-(1-butyn-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-butyl-5-and6-trifluoromethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-butyl-5-and6-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-dimethylaminosulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'- (2-n-butyl-7-cyano-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-(N-methyl-n-butylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(6-butanoylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-propionylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methane-sulphonyl)-amide

4'-(2-n-butyl-5-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-5-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methane-sulphonyl)-amide

4'-(2-n-butyl-6-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(6-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-7-methoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylmethylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

4'-(2-n-butyl-6-methoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-methoxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethane-sulphonyl)-amide

4'- (2-n-pentyl-benzimidazol-1-yl)-methyl!bi-phenyl-2-carboxylicacid-(N-trifluoromethane-sulphonyl)-amide

4'-(2-n-butyl-4-methyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-propyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5-acetamino-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-butyl-5-chloro-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5-butylaminocarbonylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-phenylaminocarbonylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-butyl-6-chloro-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5-methanesulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-ethoxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-isopropylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-4-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-dimethylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-(1-butyn-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-butyl-5-and6-trifluoromethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-butyl-5-and6-n-butylaminocarbonyl-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5-dimethylaminosulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-butyl-7-cyano-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-trifluoromethane-sulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylaminocarbonyl-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-(N-methyl-n-butylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylcarbonylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(6-n-butanoylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'- (2-n-butyl-6-propionylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid-(N-trifluoromethane-sulphonyl)-amide

4'-(2-n-butyl-5-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-5-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoro-methansulphonyl)-amide

4'-(2-n-butyl-5-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethane-sulphonyl)-amide

4'-(2-n-butyl-6-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(6-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-7-methoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-trifluoromethane-sulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylmethylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-trifluoromethanesulphonyl)-amide

4'-(2-n-butyl-6-methoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'- (2-methoxymethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(n-benzenesulphonyl)-amide

4'- (2-n-pentyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-4-methyl-7-methoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'- (2-n-propyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-5-acetamino-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'- (2-n-butyl-5-chloro-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-5-butylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-6-phenylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-4-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-5-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'- (2-n-butyl-6-chloro-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-5-methanesulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-6-ethoxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-6-isopropylsulphonamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-4-butanoylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-6-dimethylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-5,6-dimethoxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'- (2-(1-butyn-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphenyl)-amide.

4'- (2-n-butyl-5-and6-trifluoromethyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'- (2-n-butyl-5-and6-n-butylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-5-dimethylaminosulphonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'- (2-n-butyl-7-cyano-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylaminocarbonyl-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphenyl)-amide

4'-(2-n-butyl-6-(N-methyl-n-butylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylcarbonylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(6-n-butanoylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-6-propionylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(3-n-butyl-5-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphenyl)-amide

4'-(2-n-butyl-6-(N-butylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-5-(N-propanoyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzene-sulphonyl)-amide

4'-(2-n-butyl-5-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl))-amide

4'-(2-n-butyl-4-(N-methylaminocarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(6-aminothiocarbonylamino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphenyl)-amide

4'-(2-n-butyl-7-methoxy-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

4'-(2-n-butyl-6-cyclohexylmethylaminocarbonyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-benzenesulphonyl)-amide

Example 199 4'-(2-n-Butyl-6-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid x 0.75 trifluoroacetic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-formylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicand trifluoroacetic acid.

Yield: 84.0% of theoretical, p Melting point: 110°-112° C. (amorphous)C_(33l) H₃₇ N₂ O₃ x 0.75 CF₃ COOH (513.02)

Calculated: C 64.38 H 5.06 N 8.19 Found: 64.70 5.25 7.91

Example 200 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 91.9% of theoretical,

Melting point: 130°-132° C. (amorphous) C₃₈ H₄₆ N₄ O₃ x 0.5 CF₂ COOH(663.82)

Calculated: C 70.57 H 7.06 N 8.44 Found: 70.48 7.13 8.60

Example 301 4'-(2-n-Butyl-6-(N-(n-butylaminocarbonyl)cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-butylaminocarbonyl)-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 85.7% of theoretical,

Melting point: 227°-228° C. C₃₈ H₄₄ H₄ O₂ (580.77)

Calculated: C 74.48 H 7.64 N 9.45 Found: 74.32 7.70 9.50

Example 202 4'-(2-n-butyl-6-(N-methylaminocarbonyl-cyclohexyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 88.3% of theoretical,

Melting point: 204°-206° C. C₃₂ H₃₀ N₄ O₃ (536.69)

Calculated; C 73.58 N 7.11 N 10.40 Found: 73.65 6.99 10.49

Example 203 4'-(2-n-Butyl-6-(N-ethoxycarbonyl-cyclohexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-cyclohexyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicand trifluoroacetic acid.

Yield: 89.0% of theoretical,

Melting point: 239°-240° C. C₃₄ H₃₀ N₃ O₄ (553.70)

Calculated: C 73.75 H 7.10 N7.59 Found: 73.76 7.25 7.68

Example 204 4'-(2-n-Butyl-6-cyclohexylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid x 0.7 trifluoroacetic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 97.5% of theoretical,

Melting point: 117°-119° C. C₃₃ H₃₇ N₃ O₃ x 0.7 CF₃ COOH (603.49)

Calculated: C 68.46 H 6.30 N 6.98 Found: 68.80 6.60 6.73

Example 205 4'-(2-n-Butyl-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-3-carboxylicacid semi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 85.5% of theoretical,

Melting point: 181°-183° C. C₃₃ H₂₅ N₂ O₄ x 0.5 CF₃ COOH (586.61)

Calculated: C 69.62 H 4.73 N 7.16 Found: 69.70 4.81 7.31

Example 206 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid-(N-methanesulphonyl)-amide

Prepared in analogous manner to Example 198 from 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid andthionyl chloride/methanesulphon-amide.

Yield: 32.4% of theoretical,

Melting point: 127°-129° C. C₂₀ H₂₇ N₃ O₃ S (461.50)

Calculated: C 67.67 H 5.90 N 9.10 S 6.92 Found: 67.52 6.10 9.07 6.87

Example 207 4'-(2-n-Butyl-6-((5-trifluoroacetoxy-n-pentyl)-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-trifluoroacetate semi-hydrate

1.92 g (3.3 mmol) of tert.butyl 4'-(2-n-butyl-6-(tetrahydropyran-2-yl-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateare dissolved in 100 ml of ethanol and 1.9 g of Raney nickel is added.The reaction solution is then hydrogenated for 4 hours at 120° C. and100 bar hydrogen. Catalyst is then filtered off under suction and thesolvent is distilled off in vacuum. The oil residue is purified over acolumn (silicon gel; grain size: 0.063-0.2 mm), the column being elutedusing methylene chloride and increasing parts of 2-5% ethanol. Afterrotary evaporation of the appropriate fractions, the oil obtained isdissolved in a mixture of 10 ml of methylene chloride and 10 ml oftrifluoroacetic acid, and the solution is left for 18 hours at ambienttemperature. The solvent is removed by rotary evaporation, the residueis dissolved is about 50 ml of ethyl acetate and the organic phase iswashed 3 times using about 50 ml of water. The organic solution is driedusing about 20 g of magnesium sulphate, filtered off and rotaryevaporated. The product thus obtained is dried at 50° C. is vacuum.

Yield: 1.5 g (66.0% of theoretical),

Melting point: 80°-82° C. (amorphous)

Calculated: C 59.13 H 5.33 N 8.11 Found: 59.22 5.52 7.95

Example 208 4'-(2-n-Butyl-6-(N-ethoxycarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-bensylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 86.4% of theoretical,

Melting point: 218°-220° C. C₂₅ H₂₉ N₃ O₄ (561.68)

Calculated: C 74.84 H 6.28 N 7.48 Found: 74.57 6.14 7.59

Example 209 4'-(2-n-Butyl-6-(N-methylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 83.3% of theoretical,

Melting point: 247°-249° C. C₃₄ H₃₄ N₄ O₃ (546.67)

Calculated: C 74.70 H 6.27 N 10.25 Found: 74.95 6.37 10.12

Example 210 4'-(2-n-Butyl-6-(n-hexyloxycarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(n-hexyloxycarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 89.5% of theoretical,

Melting point: 243°-244° C. C₂₃ H₃₇ N₂ O₄ (527.66)

Calculated: C 72.84 H 7.07 N 7.96 Found: 72.65 7.15 7.98

Example 211 4'-(2-n-Butyl-6-(N-hexylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 6 from tert.butyl 4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 69.2% of theoretical,

Melting point: 186°-187° C. C₃₀ H₄₄ N₄ O₂ (616.80)

Calculated: C 75.94 N 7.19 N 9.08 Found: 75.85 7.24 9.14

Example 212 4'-(2-n-Butyl-6-(n-pentylamino)-benzimidazol-1-yl-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicand trifluoroacetic acid/methylene chloride.

Yield: 75% of theoretical,

Melting point: 108°-113° C. C₃₀ H₃₅ N₃ O₃ (469.62)

Calculated: C 76.73 H 7.51 N 8.94 Found: 76.56 7.40 8.91

Example 213 4'- (2-n-Butyl-6-(5,7-dioxo-1H,3H-imidazol1,5-c!thiazol-4-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(5,7-dioxo-1H,3H-imidazo-1,5-c!thiazol-6-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 95.1% of theoretical,

Melting point: 229°-239° C. C₃₀ H₂₈ N₄ O₄ S (540.64)

Calculated: C 66.65 H 5.22 N 10.36 S 5.93 Found: 66.42 5.29 10.15 6.01

Example 214 4'-(2-n-Butyl-6-((5-hydroxy-n-pentyl)-aminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid monohydrate

Prepared in analogous manner to Example 72 from ethyl 4'-(2-n-butyl-6-((5-hydroxy-n-pentyl)-aminocarbonyl-amino)-benzimidazol-1-yl)methyl!biphenyl-2-carboxylateand 2N NaOH/ethanol.

Yield: 50.0% of theoretical,

Melting point: 158°-160° C. C₂₁ H₂₉ N₄ O₄ x H₂ O (546.67)

Calculated: C 68.11 H 7.01 N 10.25 Found: 68.01 6.90 10.30

Example 215 Ethyl 4'-(2-n-butyl-6-((5-hydroxy-n-pentyl)-aminocarbonyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

7.5 g (13.5 mmol) of ethyl 4'-(2-n-butyl-6-(tetrahydro-pyran-2-ylaminocarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateare dissolved in 250 ml of ethanol and 7.5 g of Raney nickel are added.The solution is then hydrogenated in an autoclave for 2 hours at 120° C.and 100 bar of hydrogen. The catalyst is then filtered off under suctionand the solvent is distilled off in vacuum. The oily product obtained ispurified over a column (silica gel; grain size: 0.043-0.2 mm), thecolumn being eluted using ethyl acetate/petroleum ether (9/1) and usingethyl acetate/ethanol (99/1). The appropriate fractions are evaporatedin vacuum and dried at 50° C. in a vacuum drying oven.

Yield: 2.6 g (34.7% of theoretical), oil, R_(f) : 0.50 (silica gel:ethyl acetate/ethanol=9:1)

Example 216 4'-(2-n-Butyl-6-(N-(n-butanoyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-butanoyl)-n-butylamino)-benzimidazol-1-yl)methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 90.6% of theoretical,

Melting point: 234°-235° C. C₃₃ H₃₈ N₃ O₃ (525.69)

Calculated: C 75.40 H 7.48 N 7.99 Found: 75.55 7.49 8.02

Example 217 4'-(2-n-Butyl-6-(N-(4-methyloxycarbonyl-thiazolidine-3-yl-carbonyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(4-methoxycarbonyl-thiazolidin-3-ylcarbonyl)-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 92.6% of theoretical,

Melting point: 86°-88° C. (amorphous) C₃₅ H₄₀ N₄ O₃ S (628.79)

Calculated: C 66.86 H 6.41 N 8.91 S 5.10 Found: 66.68 6.40 8.50 5.41

Example 218 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-n-butyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-butylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 96.8% of theoretical,

Melting point: 106°-108° C. (amorphous) C₃₈ H₄₄ N₄ O₃ (580.77)

Calculated: C 74.45 H 7.64 N 9.65 Found: 74.54 7.65 9.50

Example 219 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-benzyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate.

Yield: 95.0% of theoretical,

Melting point: 203°-204° C. C₃₈ H₄₂ N₄ C₃ (614.79)

Calculated: C 76.19 H 6.89 N 9.11 Found: 75.93 7.04 9.34

Example 220 4'-(2-n-Butyl-6-(N-(2-trifluoromethylphenylamino-carbonyl)-methylamino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 5 from tert.butyl 4'-(2-n-butyl-6-(N-(2-trifluoromethylphenyl-aminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 72.2% of theoretical,

Melting point: 142°-144° C. C₃₄ H₃₁ F₃ N₄ O₂ x CF₃ COOH (714.67)

Calculated: C 60.52 H 4.51 N 7.84 Found: 60.3 4.48 8.03

Example 221 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-n-hexyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylamino-carbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 94.1% of theoretical,

Melting point: 177°-178° C. C₃₈ H₄₀ N₄ O₃ (608.82)

Calculated: C 74.97 H 7.95 N 9.20 Found: 74.75 8.04 9.09

Example 222 4'-(2-n-Butyl-6-(N-cyclohexylcarbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylcarbonyl-n-hexylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 92.8% of theoretical,

Melting point: 195°-197° C. C₃₈ H₄₇ H₃ O₃ (593.81)

Calculated: C 76.86 H 7.98 N 7.08 Found: 76.66 7.94 7.16

Example 223 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-n-propylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner in Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-n-propylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 93.5% of theoretical,

Melting point: 180°-182° C. C₃₅ H₄₂ N₄ O₃ (566.74)

Calculated: C 74.18 H 7.47 N 9.80 Found: 73.98 7.54 10.05

Example 224 4'-(2-n-Butyl-6-(N-cyclohexylcarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylcarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 93.8% of theoretical,

Melting point: 230°-231° C. C₃₂ H₃₇ N₃ O₃ x 0.5 H₂ O (532.68)

Calculated: C 74.41 H 7.19 N 7.89 Found: 74.59 7.14 7.70

Example 225 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-ethyl-amino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-ethylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 95.5% of theoretical,

Melting point: 185°-186° C. C₃₄ H₄₀ N₄ O₃ (552.72)

Calculated: C 73.89 H 7.29 N 10.14 Found: 73.79 7.13 10.11

Example 226 4'-(2-n-Butyl-6-(N-(n-butanoyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-butanoyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 77.8% of theoretical,

Melting point: 206°-208° C. C₃₄ H₄₁ N₃ O₃ (539.72)

Calculated: C 75.66 H 7.66 N 7.79 Found: 75.54 7.47 7.67

Example 237 4'-(2-n-Butyl-6-isopropylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-isopropylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicand trifluoroacetic acid.

Yield: 73.3% of theoretical,

Melting point: 273°-275° C. C₂₈ H₃₁ N₃ O₂ (469.58)

Calculated: C 74.18 H 6.65 H 8.95 Found: 73.93 6.66 8.84

Example 228 4'-(2-n-Butyl-6-(N-ethoxycarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 91.8% of theoretical,

Melting point: 190°-192° C. C₂₈ H₃₁ N₃ O₄ (485.58)

Calculated: C 71.73 H 6.43 N 8.65 Found: 71.60 6.40 8.69

Example 229 4'-(2-n-Butyl-6-(N-ethoxycarbonyl-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-ethoxycarbonyl-n-pentyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 86.9% of theoretical,

Melting point: 201°-203° C. C₃₃ H₃₈ N₃ O₄ (541.69)

Calculated: C 73.17 H 7.26 N 7.76 Found: 72.97 6.98 7.69

Example 230 4'-(2-n-Butyl-6-(N-(dimethylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'(2-n-butyl-6-(N-(dimethylaminocarbonyl)-benzylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 75.3% of theoretical,

Melting point: 202°-203° C. C₂₅ H₃₉ N₄ O₃ (560.69)

Calculated: C 74.98 H 6.47 N 9.99 Found: 74.89 6.24 10.02

Example 231 4'-(2,5-Di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2,5-di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 82.6% of theoretical,

Melting point: 199°-201° C. C₂₈ H₃₂ N₂ O₂ (440.58)

Calculated: C 79.06 H 7.32 N 6.36 Found: 78.87 7.29 6.58

Example 232 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 70.0% of theoretical,

Melting point: 168°-170° C. C₄₀ H₄₄ N₄ O₂ (628.81)

Calculated: C 76.40 H 7.05 N 8.91 Found: 76.31 7.26 8.79

Example 233 4'-(2-n-Butyl-6-diethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-diethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 79.4% of theoretical,

Melting point: 235°-237° C. C₃₀ H₃₄ N₄ O₃ x 7.5 CF₃ COOH (555.64)

Calculated: C 67.01 H 6.26 N 10.05 Found: 66.99 6.02 10.12

Example 234 4'-(2-n-Butyl-6-dimethylaminoacetamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid ditrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(dimethylaminoacetamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid/methylene chloride.

Yield: 75.5% of theoretical,

Melting point: 218°-220° C. C₂₉ H₃₂ N₄ O₃ x 2 CF₃ COOH (712.65)

Calculated: C 55.61 H 4.81 N 7.86 Found: 55.61 5.05 8.19

Example 235 4'-(2-n-Butyl-6-(2,2-dimethyl-propionylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(2,2-dimethyl-propionylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 67.5% % of theoretical,

Melting point: 326°-327° C. C₃₀ H₃₃ N₃ O₃ (483.61)

Calculated: C 74.51 H 6.88 N 8.69 Found: 74.32 7.06 8.58

Example 236 4'-(2-n-Butyl-6-(N-(n-hexylaminocarbonyl)-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-hexylaminocarbonyl)-N-(2-phenylethyl)-amino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 66.7% of theoretical,

Melting point: 176°-177° C. C₄₆ H₄₈ N₄ O₃ (630.83)

Calculated: C 76.16 H 7.35 N 8.88 Found: 75.97 7.44 8.98

Example 237 4'-(2,6-Di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2,6-di-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid/methylene chloride.

Yield: 75.9% of theoretical,

Melting point: 188°-190° C. C₃₀ H₃₂ N₂ O₂ (440.59)

Calculated: C 79.06 H 7.32 N 6.36 Found: 78.96 7.36 6.18

Example 238 4'-(2-n-Butyl-6-cyclopentylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclopentylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 72.2% of theoretical,

Melting point: 272°-274° C. C₃₁ H₃₃ N₃ O₃ x 0.5 H₂ O (504.63)

Calculated: C 73.79 H 6.79 N 8.33 Found: 74.00 6.91 8.25

Example 239 4'-(2-n-Butyl-6-cyclopropylcarbonylamino-benzimid-azol-1-yl)-methyl!biphenyl-2-carboxylicacid semi-hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclopropylcarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 91.7% of theoretical,

Melting point: 275°-277° C. C₂₈ H₂₉ H₃ O₂ x 0.5 H₂ O (476.57)

Calculated: C 73.09 H 6.34 N 8.82 Found: 72.97 6.50 8.52

Example 240 4'-(2-n-Butyl-6-(1-oxo-isoindolin-2-yl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

1.6 g (3 mmol) of 4'-(2-n-butyl-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate are treated with 1.6 g of the zinc power in 30 mlof glacial acetic acid under reflux. After every hour, 1.6 g of zincpower are added and heated at reflux for one hour, this takes place 2times. Excess zinc is filtered off under suction and the filtrate isrotary evaporated to dryness. The crude product is purified over asilica gel column (grain size: 0.063-0.2 mm) using ethylacetate/ethanol/ammonia (90:10:0.1 to 80:20:01.) and crystallised fromether.

Yield: 0.45 g (64.1% of theoretical),

Melting point: 214°-216° C. C₂₃ H₂₈ N₃ O₃ x CF₃ COOH (629.64)Calculated: C 66.76 H 4.80 N 6.67 Found: 66.62 5.08 6.69

Example 241 4'-(2-(1-trans-Butenyl)-6-dimethylaminocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

a) Tert.butyl 4'-(2-(1-bromobutyl)-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

10.3 g (17.6 mmol) of tert.butyl 4'-(2-n-butyl-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate,1 liter of carbon tetrachloride and 3.1 g (17.5 mmol) ofN-bromosuccinimide are irradiated using a mercury immersion lamp for 3hours while stirring. As a result of this, the internal temperatureincreases to 50° C. The greasy product obtained is then filtered off,the residue is dissolved in methylene chloride and extracted by shakingusing water. The organic phase is dried over sodium sulphate and rotaryevaporated. The crude product is purified over a silica gel column(grain size: 0.063-0.2 mm) ethyl acetate/petroleum ether (1:4).

Yield: 4.5 g (38.4% of theoretical),

b) Tert.butyl 4'-(2-(1-trans-butenyl)-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

10.8 g (16.25 mmol) of tert.butyl 4'-(2-(1-bromobutyl)-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate,110 ml of dimethylformamide and 5.1 ml (5.2 g=34.1 mmol) of1,8-diazabicyclo 5.4.0!undec-7-ene are stirred overnight at ambienttemperature. The mixture is diluted using 200 ml of ether and extractedby shaking using 2N hydrochloric acid and water. The combined acid phaseis extracted by shaking using ethyl acetate. The ethyl acetate phase isdried over sodium sulphate and, after rotary evaporation, is purifiedover a silica gel column (grain size: 0.063-0.2 mm) using ethylacetate/petroleum ether (20:80 to 30:70). The product crystallises outon evaporation of the appropriate fractions. The product is filteredunder suction and washed using ether.

Yield: 2.30 g (24.2% of theoretical),

Melting point: 232°-234° C. C₃₇ H₃₃ N₂ O₄ (583.69)

Calculated: C 76.14 N 5.70 N 7.20 Found: 75.92 5.69 7.34

c) Tert.butyl 4'-6-amino-(2-(1-trans-butenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

2.3 g (3.94 mmol) of tert.butyl 4'-(2-(1-trans-butenyl)-6-phthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate,80 ml of ethanol and 25 ml of 40% strength aqueous methylamine arestirred for 3 hours at ambient temperature. The mixture is heated for1/4 hour on a steam bath, cooled and rotary evaporated. The residue issuspended in acetone, cooled and undissolved N-methyl-phthalimide isfiltered off. The filtrate is evaporated to dryness.

Yield: 1.78 g (100% of theoretical),

Melting point: 174°-176° C.

d) Tert.butyl 4'-(2-(1-trans-butenyl)-6-dimethylamino-carbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Prepared in analogous manner to Example 8 from tert.butyl 4'-6-amino-(2-(1-trans-butenyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand dimethylcarbamoylchloride.

Yield: 82.8% of theoretical, oil, R_(f) value: 0.35 (Silica gel;methylene chloride/ethanol=19:1)

e) 4'-(2-(1-trans-Butenyl)-6-dimethylaminocarbonyl-amino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-(1-trans-butenyl)-6-dimethylamino-carbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene choride.

Yield: 66.6% of theoretical,

Melting point: 221°-223° C. C₂₀ H₂₈ N₄ O₃ x CF₃ COOH x 0.5 H₂ O (591.59)

Calculated: C 60.90 H 5.11 N 9.47 Found: 60.83 4.96 9.53

The following compounds are prepared in analogous manner to Example241c:

4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!-2-trifluoromethanesulphonamino-biphenyloil, R_(f) value: 0.30 (Silica gel: ethylacetate/ethanol/ammonia=90:10:1)

4'- (6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylicacid M.p.: 235°-237° C.

Example 242 4'-(2-(1-trans-Butenyl)-6-cyclohexylaminocarbonyl-amino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 241 from tert.butyl 4'-(2-(1-trans-butenyl)-6-cyclohexylamino-carbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 93.7% of theoretical,

Melting point: 171°-173° C. C₃₂ H₃₄ N₄ O₂ x CF₃ COOH (636.67)

Calculated: C 64.14 H 5.54 N 8.80 Found: 64.00 5.49 8.97

Example 243 Tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

1.8 g (4 mmol) of tert.butyl 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate, 30ml of glacial acetic acid and 1.85 g (1.2 mmol) ofcis-cyclohexane-1,2-dicarboxylic acid anhydride are heated at reflux forone hour with stirring. The reaction mixture is evaporated to dryness.The residue is dissolved in methylene chloride, washed until neutralusing saturated sodium bicarbonate solution, dried over sodium sulphateand rotary evaporated. The crude product is purified over a silica gelcolumn (grain size: 0.063-0.2 mm) using ethyl acetate/petroleum ether(10:90; 20:80 and 30;70).

Yield: 1.5 g (64.1% of theoretical), C₃₇ H₄₁ N₃ O₄ (591.80)

Calculated: C 75.10 H 6.98 N 7.10 Found: 74.92 7.10 6.99

The following compounds are obtained in analogous manner:

tert.butyl 4'-(2-n-butyl-6-(4,5-dimethyl-1,2,3,6-tetrahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.30 (Silica gel; ethyl acetate/petroleum ether=1:1)

tert.butyl 4'-(2-n-butyl-6-(3,4-dimethoxy-phthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Yield: 33.8% of theoretical,

Melting point: 238°239° C.

tert.butyl 4'-(2-n-butyl-6(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (Silica gel: ethyl acetate/petroleum ether=4:1)

4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyloil, R_(f) value: 0.55 (Silica gel: ethyl acetate/petroleumether/ammonia=80:20:1)

tert.butyl 4'- (2-n-butyl-6-(endo-bicyclo2.2.2!oct-5-ene-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

M.p.: 180°-182.5° C.

tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.43 (Silica gel: ethyl acetate/petroleum ether=2:1)

tert.butyl 4'- (2-n-butyl-6-(methyl-5-norbornene-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(trans-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateM.p.: 168°-170° C.

tert.butyl 4'-(2-n-butyl-6-(3,6-endoxo-1,2,3,6-tetrahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'- (2-n-butyl-6-(cis-5-norbornene-endo-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate M.p.:179°-180° C.

4'-(2-n-Butyl-5-(N-cyclohexylaminocarbonyl-methylamine)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyloil, R_(f) value: 0.45 (Silica gel: ethyl acetate/petroleumether/ammonia=90:10:1)

4'-(2-n-Butyl-5-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyloil, R_(f) value: 0,35 (Silica gel: ethyl acetate/petroleum ether=4:1)

Example 244 4'-(2-n-Butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 58.8% of theoretical,

Melting point: 270° C. (decomposition) C₂₃ H₃₃ N₃ O₄ x CF₃ COOH (649.68)

Calculated: C 64.71 H 5.28 N 6.47 Found: 64.76 5.41 6.65

Example 245 4'-(2-n-Butyl-6-(4,5-dimethyl-1,2,3,6-tetrahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(4,5-dimethyl-1,2,3,6-tetrahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 30% of theoretical,

Melting point: 219°-221° C. C₃₅ H₃₅ N₃ O₄ x H₂ O (579.69)

Calculated: C 72.52 H 6.43 N 7.23 Found: 72.66 6.49 7.43

EXAMPLE 246 4'-(2-n-Butyl-6-(3,4-dimethoxy-phthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid dihydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3,4-dimethoxy-phthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 24.3% of theoretical,

Melting point: 206°-208° C. C₃₃ H₃₁ N₃ O₆ x 2 H₂ O (625.68)

Calculated: C 67.19 H 5.64 N 6.72 Found: 67.22 5.84 6.97

Example 247 4'-(2-n-Butyl-6-(N-(dimethylaminocarbonyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(dimethylaminocarbonyl)-n-pentylamino)-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride

Yield: 81.8% of theoretical,

Melting point: 174°-176° C. C₃₃ H₄₀ N₄ O₃ x CF₃ COOH (654.73)Calculated: C 64.21 H 6.31 N 8.55 Found: 64.38 6.28 8.64

Example 248 4'-(2-n-Butyl-6-(N-(4-phenylamino-n-butyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(4-phenylamino-n-butyl)-n-pentylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Example 249 4'-(2-n-Butyl-6-cyclohexylaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-(1N-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 58b from 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyland cyclohexyliscyanate in methylene chloride

Melting point: 232°-234° C. C₃₂ H₃₈ N₈ O (548.69)

Calculated: C 70.05 H 6.61 N 20.42 Found: 69.86 6.66 20.25

Example 250 4'-(2-n-Butyl-6-dimethylaminoaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 58b from 4'-(2-n-butyl-4-dimethylaminoaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyland hydrochloric acid in ether/methanol/methylene chloride.

Yield: 69.8% of theoretical,

Melting point: 239°-241° C. C₂₆ H₃₀ N₂ O (494.60)

Calculated: C 67.99 H 6.11 N 22.65 Found: 67.85 6.08 22.55

Example 251 4'-(2-n-Butyl-6-(N-cyclohexylaminoaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenylhydrate

Prepared in analogous manner to Example 58 from 4'-(2-n-butyl-6-methylamino-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyland cyclohexylisocyanate.

Yield: 97.5% or theoretical

Melting point: 163°-165° C. C₃₃ H₃₈ N₈ O x H₂ O (580.75)

Calculated: C 68.25 H 6.94 N 19.30 Found: 68.43 6.90 19.15

Example 252 4'-(2-n-Butyl-6-cyclohexylaminoaminocarbonylamino-benzimidazol-1-yl)-methyl!-2-trifluoromethanesulphonamino-biphenyl

Prepared in analogous manner to Example 7 from 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!-2-trifluoromethanesulphonamino-biphenyland cyclohexylisocyanate.

Yield: 90.9% of theoretical,

Melting point: 163°-165° C. C₃₂ H₃₈ N₂ O₃ S (627.73)

Calculated: C 61.23 H 5.78 N 11.15 Found: 61.12 5.67 11.29

Example 253 4'-(2-n-Butyl-6-cyclohexylaminocarbonyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexylaminocarbonyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 80.0% of theoretical,

Melting point: 218°-219° C. C₃₂ H₃₅ N₂ O₄, (525.65)

Calculated: C 73.12 H 6.71 N 7.99 Found: 73.04 6.84 7.92

Example 254 4'-(2-n-Butyl-6-cyclohexyloxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-cyclohexyloxycarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 90.9% of theoretical,

Melting point: 238°-240° C. C₃₂ H₃₅ N₃ O₄ (525.65)

Calculated: C 73.12 H 6.71 N 7.99 Found: 73.18 6.74 8.11

Example 255 4'-(2-n-Butyl-6-morpholinocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-morpholinocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 85.0% of theoretical,

Melting point: 278°-279° C. C₃₀ H₃₂ N₄ O₄ (512.61)

Calculated: C 70.29 H 6.29 N 10.93 Found: 70.28 6.28 11.00

Example 256 4'-(2-n-Butyl-6-pyrrolidinocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-pyrrolidinocarbonylamino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Example 257 4'-(2-n-Butyl-6-(N-methylaminocarbonyl-N-(3-cyclohexyl-n-propyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-methylaminocarbonyl-N-(3-cyclohexyl-n-propyl)-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 84.8% of theoretical,

Melting point: 215°-216° C. C₃₈ H₄₄ N₄ O₃ (580.72)

Calculated: C 74.45 H 7.64 N 9.65 Found: 74.52 7.75 9.76

Example 258 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-3-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-2-phenylnaphthalene-3-carboxylateand trifluoroacetic acid.

Yield: 57% of theoretical,

Melting point: fused from 100° C. C₂₈ H₂₈ N₂ O₂ (434.54)

Calculated: C 80.34 H 5.81 N 6.46 Found: 80.63 5.89 6.28

Example 259 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-1-phenyl-naphthalene-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-1-phenyl-naphthalene-2-carboxylateand trifluoroacetic acid.

Yield: 42.5% of theoretical,

Melting point: 218°-220° C. C₂₈ H₂₈ N₂ O₂ (434.54)

Calculated: C 80.34 H 5.81 N 6.46 Found: 80.18 6.01 6.85

Example 260 4'(2-n-Butyl-6-(cis-hexahydrophthalimino-benzimidazol-1-yl)-methyl!-1-(1H-tetrazol-5-yl)-2-phenyl-naphthalene

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-(cis-hexahydrophthalimino-benzimidazol-1-yl)-methyl!-1-cyano-2-phenyl-naphthaleneand ammonium chloride/sodium azide.

Example 261 4'-(2-n-Propyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-1-(1H-tetrazol-5-yl)-2-phenyl-naphthalene

Prepared in analogous manner to Example 55 from 4'-(2-n-propyl-6-(N-cyclohexylaminocarbonyl-methyl-amino)-benzimidazol-1-yl)-methyl!-1-cyano-2-phenyl-naphthaleneand ammonium chloride/sodium azide.

Example 262 4'-(2-n-Propyl-6-(N-cyclohexylaminocarbonyl-methyl-amino)-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylicacid

Prepared n analogous manner to Example 9 from tert.butyl 4'-(2-n-propyl-6-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylateand trifluoroacetic acid.

Yield: 73.0% of theoretical,

Melting point: 193°-195° C. C₃₀ H₃₈ N₄ O₃ (574.70) Calculated: C 75.28 H6.67 N 9.75 Found: 75.10 6.71 9.72

Example 263 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylateand trifluoroacetic acid.

Yield: 89.0% of theoretical,

Melting point: 228°-230° C. C₂₈ H₂₈ N₂ O₂ (434.51)

Calculated: C 80.16 H 6.03 N 6.45 Found: 80.11 6.00 6.30

Example 264 4'-(2-n-Butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylateand trifluoroacetic acid.

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-phenyl-naphthalene-1-carboxylateand trifluoroacetic acid.

Yield: 37.0% of theoretical,

Melting point: 215°-218° C. C₂₈ H₃₃ N₃ O₄ (571.65)

Calculated: C 75.63 H 5.82 N 7.35 Found: 75.47 5.63 7.11

Example 265 4'-(2-n-Butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylicacid.

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-Butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 63.0% of theoretical,

Melting point: 198°-200° C. C₂₃ H₃₂ BrN₃ O₄ (614.56)

Calculated: C 64.50 H 5.25 N 6.84 Br 13.00 Found: 64.38 5.22 6.73 13.05

Example 266 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylic acid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylate andtrifluoroacetic acid.

Yield: 88% of theoretical,

Melting point: 209°-211° C. C₂₈ H₃₂ BrH₂ O₂ (463.39)

Calculated: C 64.80 H 5.00 N 6.05 Br 17.25 Found: 64.68 5.14 5.97 17.26

Example 267 4'-(2-n-Butyl-benzimidazol-1-yl)-methyl!-5-chloro-biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-benzimidazol-1-yl)-methyl!-5-chloro-biphenyl-2-carboxylateand trifluoroacetic acid.

Yield: 74% of theoretical,

Melting point: 188°-190° C. C₂₃ H₂₃ ClN₂ O₂ (418.91)

Calculated: C 71.67 N 5.53 N 6.69 Found: 71.49 5.52 6.66

Example 268 4'-(2-n-Butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyland ammonium chloride/sodium azide.

Yield: 25.0% of theoretical,

Melting point: >125° C. C₂₃ H₃₀ ClN₇ O₂ (594.11)

Calculated: C 66.71 H 5.43 N 16.50 Cl 5.87 Found: 66.54 5.63 16.35 5.91

Example 269 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonyl-methyl-amino)-benzimidazol-1-yl)-methyl!-4-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(N-cyclohexylaminocarbonyl-methyl-amino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyland ammonium chloride/sodium azide.

Example 270 4'-(2-n-Butyl-6-(N-(n-dodecylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid trifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-dodecylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateis trifluoroacetic acid/methylene chloride.

Yield: 85.7% of theoretical,

Melting point: 61°-62° C. C₃₂ H₃₂ N₄ O₃ x CF₃ COOH (738.39) Calculated:C 66.65 H 7.23 N 7.58 Found: 66.68 7.47 7.83

Example 271 4'-(2-n-Butyl-6-(N-(cyclohexylaminocarbonyl)-n-octylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 72 from ethyl 4'-(2-n-butyl-6-(N-(cyclohexylamino-carbonyl)-n-octylamino)-benzimidazol-1-yl)-methyl)bi-phenyl-2-carboxylatein ethanol/2N sodium hydroxide solution.

Yield: 94.9% of theoretical.

Melting point: 151°-152° C. C₄₀ H₃₂ N₄ O₂ (636.88)

Calculated: C 75.44 H₈.23 N 8.80 Found: 75.63 8.37 8.92

Example 2724'(2-n-Butyl-6-(N-(n-octylaminocarbonyl)-methyl-amino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(N-(n-octylaminocarbonyl)-methylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateis trifluoroacetic acid/methylene chloride.

Yield: 87.5% of theoretical

Melting point: 169°-170° C. C₃₃ H₄₄ N₄ O₃ (568.76)

Calculated: C 73.91 H 7.80 N 9.85 Found: 73.98 7.95 9.78

Example 273 4'-(2-n-Butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 58 from 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyland hydrochloric acid in ether/methanol/methylene chloride.

Yield: 47.6% of theoretical,

Melting point: 147°-149° C. C₃₃ H₃₃ N₇ O₂ (559.67)

Calculated: C 70.82 N 5.94 N 17.52 Found: 70.61 6.12 17.63

Example 274 4'- (2-n-Butyl-6-(endo-bicyclo2.2.2!oct-5-one-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylic acidtrifluoroacetate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(endo-bicyclo 2.2.2!oct-5-ene-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 88.6% of theoretical,

Melting point: 161°-163° C. C₂₅ H₃₃ H₃ O₄ x CF₃ COOH (673.69)Calculated: C 65.96 N 5.08 N 6.23 Found: 75.72 4.99 6.11

Example 275 4'- (2-n-Butyl-6-(methyl-5-norbornene-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acid (isomermixture)

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(methyl-5-norbornene-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate (isomermixture) and trifluoroacetic acid in methylene chloride.

Yield: % of theoretical, Melting point: -°C. C H N O (. )

Calculated: C . H . N . Found: . . .

Example 276 4-'(2-n-Butyl-6-(trans-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid dihydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(trans-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 60.7% of theoretical,

Melting point: 188°-190° C. C₃₃ H₃₃ N₃ O₄ x 2 H₂ O (571.47)

Calculated: C 69.33 H 6.52 N 7.35 Found: 69.48 4.40 7.57

Example 277 4'-(2-n-Butyl-6-(3.6-endoxo-1,2,3,6-tetrahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3,6-endoxo-1,2,3,6-tetrahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: % of theoretical,

Melting point: -°C. C H N O (. )

Calculated: C . H . N . Found: . . .

Example 278 4'- (2-n-Butyl-6-(cis-5-norbornene-endo-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)methyl!biphenyl-2-carboxylic acidmonohydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis-5-norbornene-endo-2,3-dicarboxylicacid-imino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 22.1% of theoretical,

Melting point: 263°-265° C. C₃₄ H₃₁ N₂ O₄ x H₂ O (563.65)

Calculated: C 72.44 H 5.90 N 7.45 Found: 72.28 5.81 7.46

Example 279 5'-(2-n-Butyl-6-(2-carboxyl-cyclohexylcarbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

0.6 g (1.5 mmol) of 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylic acidare dissolved in 150 ml of methylene chloride with heating and cooled toambient temperature. After the addition of 240 mg (1.55 mmol) ofcis-cyclohexan-1,2-dicarboxylic acid anhydride the mixture is stirredfor 5 hours at ambient temperature. The reaction product whichcrystallises out is suction filtered, washed with methylene chloride anddried in a vacuum drying chamber at 50° C.

Yield: 0.58 g (69.8% of theory),

Melting point: 186°-188° C.

Yield: 0.58 g (69.8% of theory),

Melting point: 186°-188° C. C₃₂ H₃₉ N₃ O₃ (553.66)

Calculated: C 71.59 H 6.37 N 7.59 Fund: 71.42 4.56 7.56

Example 280 4'-(2-n-Butyl-6-(2-carboxy-cyclohexylcarbonylamino)-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-4-bromo-biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 88% of theory,

Melting point: from 145° C. (decomp.) C₃₃ H₃₄ BrN₂ O₃ (632.58)

Calculated: C 62.66 H 8.42 Br 12.63 N 6.64 Found: 62.50 5.33 12.78 6.43

Example 281 4'-(2-n-Butyl-6-(3-carboxy-cis-5-norbornene-endo-2-carbonylamino)-benzimidazol-1-yl)-methyl!biphenyl-3-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(cis-5norbornene-endo-3,3-dicarboxylic acidimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate andtrifluoroacetic acid in methylene chloride.

Yield: 17.1% of theory,

Melting point: 199°-201° C. C₃₄ H₃₉ N₂ O₃ (563.66)

Calculated: C 73.44 H 5.90 N 7.48 Found: 72.26 5.82 7.44

Example 282 4'(2-n-Butyl-6-dimethylaminocarbonyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.-butyl 4'(2-n-butyl-6-dimethylaminocarbonyloxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 81.9% of theory.

Melting point: 241°-242° C. C₂₈ H₂₉ N₂ O₄ (471.56)

Calculated: C 71.32 N 6.20 N 8.91 Found: 71.15 6.28 8.09

Example 283 4'-(2-n-Butyl-6-(N-acetyl-n-octylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.-butyl 4'-(2-n-butyl-6-(N-acetyl-n-octylamino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Yield: 77.2% of theory,

Melting point: 192°-193° C. C₃₉ H₄₃ N₃ O₃ (583.74)

Calculated: C 75.92 H 7.83 N 7.59 Found: 75.75 8.03 7.45

Example 284 Tert.-butyl 4'-(2-n-butyl-6-(2phenylethylamino-carbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

484 mg (1 mmol) of tert.-butyl 4'-(2-n-butyl-6-carboxy-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateare dissolved in 10 ml of absolute tetrahydrofuran and cooled to -20° C.with stirring and cooling with dry ice/isopropanol. At this temperature101 mg (1 mmol) of N-methylmorpholine are added. The resulting mixtureis then cooled to -30° C. and a solution of 136 mg (1 mmol) ofisobutylchloroformate dissolved in 5 ml of absolute tetrahydrofuran isslowly added dropwise. To complete the formation of the mixed anhydridethe mixture is stirred for a further hour at -40° C. At -40° C. 134 mg(1.1 mmol) of 2-phenylethylamine dissolved in 2 ml of absolutetetrahydrofuran are slowly added dropwise. Then the mixture is allowedto rise slowly to ambient temperature and stirred for 16 hours atambient temperature. The solvent is distilled off, the remaining viscousoil is taken up in saturated common salt solution/ethyl acetate andextracted 3 times in all with ethyl acetate. The ethyl acetate phasesare dried over sodium sulphate and evaporated down. The viscous oil isdissolved in methylene chloride and purified over a silicon gel column(eluant: methylene chloride/ethanol 50:1 and 25:1).

Yield: 505 mg (86% of theory), oil, R_(f) value: 0.5 (silica gel:ethanol/methylene chloride=1:19) C₃₈ H₄₁ N₃ O₂ (587.80)

Calculated: C 77.65 H 7.03 N 7.15 Found: 77.58 7.24 7.34

The following compounds are obtained analogously:

tert.butyl 4'-(2-n-butyl-6-(2-phenylamino-ethylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.45 (silica gel: ethanol/methylene chloride=1:19)

tert.butyl 4'- (2-n-butyl-6-(5-carboxy-n-pentylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

Melting point: 166°-167° C.

Example 285 4'-(2-n-butyl-6-(2-phenylethylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(2-phenylethylamino-carbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 19.7% of theory,

Melting point: 208°210° C. C₃₄ H₃₃ W₂ O₂ (531.65)

Calculated: C 76.81 H 6.26 N 7.90 Found: 76.69 6.48 7.92

Example 286 4'-(2-n-Butyl-6-(2-phenylaminoethylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid x 1.8 HCl

Prepared analogously to Example 9 from tert.butyl 4'-(2-n-butyl-6-(2-phenylaminoethylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 30% of theory,

Melting point: 240°-242° C. C₃₆ H₃₄ W₄ O₃ ×1.5 HCl (601.36)

Calculated: C 67.91 H 5.95 N 9.32 Found: 67.88 5.93 9.15

Example 287 4'-(2-n-Butyl-6-(5-carboxy-n-pentylaminocarbonyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(5-carboxy-n-pentylamino-carbonyl)-benzimidazol-1-yl)methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 37.4% of theory,

Melting point: from 114° C. (decomp.) C₃₇ H₃₅ N₃ O₃ (541.70)

Calculated: C 70.96 H 6.51 N 7.76 Found: 70.84 6.42 7.85

Example 288 4'-(2-n-Butyl-6-(2-carboxy-propionyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 72 from methyl 4'-(2-n-butyl-6-(2-carboxy-propionyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand sodium hydroxide solution/methanol.

Example 289 Tert.butyl 4'-(2-n-butyl-6-homophthalimino-benzimidazol-1-yl)-methyl!-biphenyl-2-carboxylate

1.5 g (3.3 mmol) of tert.butyl 4'-(6-amino-2-n-butyl-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate and0.6 g (3.63 mmol) of homophthalic acid anhydride are refluxed for 20hours in 20 ml of pyridine. Then the solvent is removed in vacuo and theresidue is purified over a silica gel column (particle size 0.063-0.2mm; eluant; methylene chloride/ethanol=100:2, 100:3 and 100.5).

Yield: 15.2% of theory,

Melting point: 109°112° C. C₃₈ H₃₇ N₃ O₄ (599.73)

Calculated: C 76.10 H 6.22 N 7.01 Found: 75.90 6.28 6.90

The following compounds are obtained analogously:

tert.butyl 4'(2-n-butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(3,3-pentamethylene-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(7-methoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(3-n-butyl-6-(4,4-dimethyl-7-methoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2carboxylate

tert.butyl 4'-(2-n-butyl-6-(6,7-dimethoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.buytl 4'-(2-n-butyl-6-(6,7-dimethoxy-4,4-dimethyl-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-glutarimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(3,3-dimethyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(3-ethyl-3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

4'-(2-n-butyl-6-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyl

tert.butyl 4'-(2-n-butyl-6-(4,4-dimethyl-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylate

tert.butyl 4'-(2-n-butyl-6-(5-methyl-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateoil, R_(f) value: 0.75 (Silica gel: ethyl acetate/petroleum ether=4:1)

Example 290 4'-(2-n-Butyl-6-homophthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-homophthalimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 79% of theory,

Melting point: 171°-173° C. C₃₄ H₂₉ N₃ O₄ (543.62)

Calculated: C 75.12 H 5.38 N 7.73 Found: 74.95 5.18 7.64

Example 291 4'-(2-n-Butyl-6-(4,4-dimethyl-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid hydrate

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(4,4-dimethyl-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 77.4% of theory,

Melting point: 299°301° C. C₃₆ H₃₃ N₃ O₄ ×H₂ O (589,69)

Calculated: C 73.33 H 5.98 N 7.13 Found: 73.60 6.14 7.33

Example 292 4'-(2-n-Butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 40% of theory,

Melting point: 191°-194° C. C₃₄ H₃₅ N₃ O₄ (549.64)

Calculated: C 72.29 H 6.42 N 7.65 Found: 74.08 6.31 7.52

Example 293 4'-(2-n-Butyl-6-(3,3-pentamethylene-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2--butyl-6-(3,3-antamethylene-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 31% of theory,

Melting point: 182°-185° C. C₃₅ H₃₇ N₃ O₄ (563.67)

Calculated: C 74.57 H 6.62 N 7.46 Found: 74.43 6.52 7.32

Example 294 4'-(2-n-Butyl-6-(cis-hexahydro-phthalimino)-benzimidazol-1-yl)-methyl!-5-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(cis-hexahydro-phthalimino)-benzimidazol-1-yl)-methyl!-5-chloro-2-cyano-biphenyland sodium azide/ammonium chloride.

Yield: 22% of theory,

Melting point: from 135° C. (sintering) C₃₃ H₃₂ ClN₂ O₃ (594.10)

Calculated: C 66.71 H 5.43 N 16.50 Cl 5.97 Found: 66.51 5.39 16.77 5.92

Example 295 4'-(2-n-Butyl-6-(N-cyclohexylaminocarbonylamino)-benzimidazol-1-yl)-methyl!-5-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(3-n-butyl-6-(N-cyclohexylaminocarbonylamino)-benzimidazol-1-yl)-methyl!-5-chloro-2-cyano-biphenyland sodium azide/ammonium chloride.

Example 296 4'-(2-n-Butyl-6-(7-methoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(7-methoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid.

Example 297 4'-(2-n-Butyl-6-(4,4-dimethyl-7-methoxy-homophthalimino)-benzimidazol-2-yl)-methoxyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(4,4-dimethyl-7-methoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 60,1% of theory,

Melting point: 104°-105° C. C₃₇ H₃₅ N₃ O₃ (601.70)

Calculated: C 73.86 H 5.86 N 6.98 Found: 73.92 6.04 7.11

Example 298 4'-(2-n-Butyl-6-(6,7-dimethoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(6,7-dimethoxy-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Example 299 4'-(2-n-Butyl-6-(6,7-dimethoxy-4,4-dimethyl-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(6.7-dimethoxy-4,4-dimethyl-homophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Example 300 4'-(2-n-Butyl-6-(3,3-pentamethylene-glutarimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3,3-pentamethylene-glutarimino)-benzimidazol-1-yl)-methyl!-2-cyano-biphenyland sodium azide/ammonium chloride.

Yield: 29% of theory,

Melting point: from 140° C. (sintering) C₂₅ H₂₇ N₂ O₃ (587.70)

Calculated C 71.52 H 6.25 N 16.68 Found: 71.37 6.20 16.71

Example 301 4'-(2-n-Butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!-2-(1N-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!-2-cyano-biphenyland medium azide/ammonium chloride.

Yield: 31% of theory,

Melting point: from 166° C. (sintering) C₃₆ H₂₉ N₇ O₂ (573.68)

Calculated: C 71.18 H 6.18 N 17.09 Found: 71.10 6.22 17.20

Example 302 4'-(2-n-Butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3,3-tetramethylene-glutarimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyland sodium azide/ammonium chloride.

Example 303 4'-(2-n-Butyl-6-glutarimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.-butyl 4'-(2-n-butyl-6-glutarimino-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 82% of theory,

Melting point: >220° C. C₃₀ H₂₉ N₃ O₄ (495.56)

Calculated: C 72.71 H 5.90 N 8.45 Found: 72.56 5.79 8.22

Example 304 4'-(2-n-Butyl-6-glutarimino-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-glutarimino-benzimidazol-1-yl)-methyl!-2-cyano-biphenyl andsodium azide/ammonium chloride.

Yield: 47% of theory,

Melting point; from 139° C. (sintering) C₃₀ H₂₉ N₇ O₂ (519.59)

Calculated: C 69.34 H 5.62 N 18.87 Found: 69.30 5.52 18.69

Example 305 4'-(2-n-Butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 39% of theory,

Melting point: >220° C. C₃₁ H₃₁ N₃ O₄ (509.58)

Calculated: C 73.06 H 6.13 N 8.25 Found: 72.91 5.88 8.02

Example 306 4'-(2-n-Butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-2-cyano-biphenyland sodium azide/ammonium chloride.

Yield: 28% of theory.

Melting point: from 157° C. (sintering) C₃₁ H₃₁ N₇ O₃ (533.61)

Calculated: C 69.77 H 5.86 N 18.38 Found: 69.69 5.81 18.16

Example 307 4'-(2-n-Butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyland sodium azide/ammonium chloride.

Example 308 4'-(2-n-Butyl-6-(3,3-dimethyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3,3-dimethyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 41% of theory,

Melting point: >220° C. C₃₂ H₃₃ N₃ O₄ (523.61)

Calculated: C 73.40 H 6.35 N 8.03 Found: 73.29 6.21 7.91

Example 309 4'-(2-n-Butyl-6-(3,3-dimethyl-glutarimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3,3-dimethyl-glutarimino)-benzimidazol-1-yl)-methyl!-2-cyano-biphenyland sodium azide/ammonium chloride.

Yield: 29% of theory,

Melting point: from 151° C. (sintering) C₃₂ H₃₃ N₇ O₂ (547.64)

Calculated: C 70.18 H 6.07 N 17.91 Found: 69.91 5.98 17.85

Example 310 4'-(2-n-Butyl-6-(3-ethyl-3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(3-ethyl-3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 58% of theory,

Melting point: >220° C. C₃₂ H₃₉ N₃ O₄ (537.63)

Calculated: C 73.72 H 6.56 N 7.82 Found: 73.55 6.41 7.76

Example 311 4'-(2-n-Butyl-6-(3-ethyl-3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3-ethyl-3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-2-cyano-biphenyland sodium azide/ammonium chloride.

Yield: 26% of theory,

Melting point: from 138° C. (sintering) C₃₃ H₃₅ N₇ O₂ (561.67)

Calculated: C 70.56 H 6.28 N 17.46 Found: 70.47 6.02 17.33

Example 312 4'-(2-n-Butyl-6-(3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 59 from 4'-(2-n-butyl-6-(3-ethyl-3-methyl-glutarimino)-benzimidazol-1-yl)-methyl!-4-chloro-2-cyano-biphenyland sodium azide/ammonium chloride.

Example 313 4'-(2-n-Butyl-5-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 58b from 4'-(2-n-butyl-5-(N-cyclohexylaminocarbonyl-methylamino)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyland hydrochloric acid in methylene chloride/ether/methanol.

Yield: 76.2% of theory,

Melting point: 150°-152° C. C₃₃ H₃₈ H₈ O (562.72)

Calculated: C 70.44 H 6.80 N 19.91 Found: 70.32 7.05 19.76

Example 314 4'-(2-n-Butyl-6-(5-methyl-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid

Prepared in analogous manner to Example 9 from tert.butyl 4'-(2-n-butyl-6-(5-methyl-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylateand trifluoroacetic acid in methylene chloride.

Yield: 37% of theory,

Melting point: 143°-144° C. C₃₄ H₃₅ N₃ O₄ (549.67)

Calculated: C 74,29 H 6,42 N 7,62 Found: 74,47 6,67 7,55

Example 315 4'-(2-n-Butyl-5-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1H-tetrazol-5-yl)-biphenyl

Prepared in analogous manner to Example 58 from 4'-(2-n-butyl-5-(cis-hexahydrophthalimino)-benzimidazol-1-yl)-methyl!-2-(1-triphenylmethyl-tetrazol-5-yl)-biphenyland hydrochloric acid/ethanol.

Yield: 59.5% of theory,

Melting point: 230°-232° C. C₃₃ H₃₃ H₇ O₂ (559,67)

Calculated: C 70,82 H 5,94 H 17,52 Found: 70.64 6.10 17.72

Example 316 4'-(2-n-Butyl-5-(2-carboxymethyl-propionyl)-benzimidazol-1-yl)-methyl!biphenyl-2-carboxylicacid x 0.25 H₂ O

Prepared is analogous manner to Example 72 from methyl 4'-(2-n-butyl-5-(2-carboxymethyl-propionyl)-benzimidazol-1-yl(-methyl!biphenyl-2-carboxylateand aquous sodium hydroxide/ethanol.

Yield: 25% of theory

Melting point: 223°-225° C. C₃₀ H₃₀ N₂ O₅ x H₂ O (503,08)

Calculated: C 71,62 H 6,11 N 5,56 Found: 71,56 6,14 5,58

Each suitable compound of the formula I, for example the compounds ofthe above examples, may be used as active substance in the followingpharmaceutical application examples:

Example I

Ampoules containing 50 mg of active ingredient per 5 ml

    ______________________________________    Active ingredient      50    mg    KH.sub.2 PO.sub.4      2     mg    Na.sub.2 HPO.sub.4 × 2H.sub.2 O                           50    mg    NaCl                   12    mg    Water for injections ad                           5     ml    ______________________________________

Preparation

The buffer substances and the isotonic agent are dissolved in part ofthe water. The active ingredient is added and after it is completelydissolved, the solution is made up to the nominal volume with water.

Example II

Ampoule containing 100 mg of action ingredient per 5 ml

    ______________________________________    Active ingredient        100    mg    Methylglucamine          35     mg    Glycofurol               1,000  mg    Polyethylene glycol-polypropylene glycol                             250    mg    block polymer    Water for injections ad  5      ml    ______________________________________

Preparation

Methylglucamine is dissolved in part of the water and the activeingredient is dissolved with stirring and heating. After adding thesolvent, the solution is made up to the nominal volume with water.

Example III

Tablets containing 50 mg of active ingredient

    ______________________________________    Active ingredient      50.0   mg    Calcium phosphate      70.0   mg    Lactose                40.0   mg    Corn starch            35.0   mg    Polyvinylpyrrolidone   3.5    mg    Magnesium stearate     1.5    mg                           200.0  mg    ______________________________________

Preparation

The active ingredient, CaHPO₄, lactose and corn starch are moistenedevenly with an aqueous PVP solution. The mixture is passed through a 2sieve, dried at 50° C. is an oven with circulating air and sieved again.

After admixing the lubricant, the granules are pressed on a tabletingmachine.

Example IV

Coated tablets containing 50 mg of active ingredient

    ______________________________________    Active ingredient     50.0   mg    Lysine                25.0   mg    Lactose               60.0   mg    Corn starch           34.0   mg    Gelatine              10.0   mg    Magnesium stearate    1.0    mg                          180.0  mg    ______________________________________

Preparation

The active ingredient is mixed with the auxiliaries and moistened withan aqueous gelatine solution. After sieving and drying, the granules aremixed with magnesium stearate and pressed to form cores.

The cores thus prepared are coated with a shell in accordance with knownprocesses. Dyestuff may be added to the coating suspension or solution.

Example V

Coated tablets containing 100 mg of active ingredient

    ______________________________________    Active ingredient      100.0  mg    Lysine                 50.0   mg    Lactose                86.0   mg    Corn starch            50.0   mg    Polyvinylpyrrolidone   2.8    mg    Microcrystalline celluse                           60.0   mg    Magnesium stearate     1.2    mg                           350.0  mg    ______________________________________

Preparation

The active ingredient is mixed with the auxiliaries and moistened withan aqueous PVP solution. The moist mixture is passed through a 1.5 mmsieve and dried at 45° C. After drying, the mixture is sieved again andthe magnesium stearate is admixed. This mixture is pressed to formcores.

The cores thus prepared are coated with a shell in accordance with knownprocesses. Dyestuffs may be added to the coating suspension or solution.

Example VI

Capsules containing 250 mg of active ingredient

    ______________________________________    Active ingredient     250.0  mg    Corn starch           68.5   mg    Magnesium stearate    1.5    mg                          320.0  mg    ______________________________________

Preparation

Active ingredient and corn starch are mixed and moistened with water.The moist mixture is sieved and dried. The dry granules are sieved andmixed with magnesium stearate. The final mixture is placed in size 1hard gelatine capsules.

Example VII

Oral suspension containing 50 mg of active ingredient per 5 ml

    ______________________________________    Active ingredient      50.0   mg    Hydroxyethylcellulose  50.0   mg    Sorbic acid            5.0    mg    Sorbitol 70% strength  600.0  mg    Glycerol               200.0  mg    Flavor                 15.0   mg    Water ad               5.0    ml    ______________________________________

Preparation

Distilled water is heated to 70° C. Hydroxyethylcellulose is dissolvedin the water with stirring. The solution is cooled to ambienttemperature by adding sorbitol solution and glycerol. Sorbic acid,flavour and active ingredient are added at ambient temperature. Air isremoved from the suspension by evacuating while stirring. 5.0 mlcontains one dose=50 mg.

Example VIII

Suppositories containing 100 mg of active ingredient

    ______________________________________    Active ingredient    100.0   mg    Solid lard           1,600.0 mg                         1,700.0 mg    ______________________________________

Preparation

The hard fat is melted. The ground active substance is dispersedhomogeneously in the melt at 40° C. The mixture is cooled to 38° C. andpoured into slightly pre-cooled suppository moulds.

We claim:
 1. A compound of the formula I ##STR22## wherein R₁ representa carboxy or C₁₋₃ -alkoxycarbonyl group,R₂ represents a hydrogen atom ora methyl group, R₃ represents a n-C₃₋₅ alkyl group wherein one methylenegroup may be replaced by an oxygen or sulphur atom, R₄ represents acarboxy or 1H-tetrazolyl group, R₅ and R₆ each represents a hydrogenatom, or a pharmaceutically acceptable salt thereof.
 2. A compound ofthe formula I according to claim 1, whereinR₁ represent a carboxy,methoxycarbonyl, ethoxycarbonyl or n-propoxycarbonyl group, R₂represents a hydrogen atom or a methyl group, R₃ represents an C₂₋₄-alkoxy or C₂₋₄ -alkylthio group, R₄ represents a carboxy or1H-tetrazolyl group, R₅ and R₆ each represents a hydrogen atom, or apharmaceutically acceptable salt thereof.
 3. 4'-(2-Ethylthio-benzimidazolyl-1-yl)-methyl!-biphenyl-2-carboxylic acid ora pharmaceutically acceptable salt thereof.